Author: "Marie Josèphe Giraud-Panis" - Searchworks@Jio Institute Digital Library Search Results

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49 results on '"Marie Josèphe Giraud-Panis"'

1. Innovative Tools for DNA Topology Probing in Human Cells Reveal a Build-Up of Positive Supercoils Following Replication Stress at Telomeres and at the FRA3B Fragile Site

Author: Claire Ghilain, Olivia Vidal-Cruchez, Aurélia Joly, Michelle Debatisse, Eric Gilson, and Marie-Josèphe Giraud-Panis
Subjects: DNA topology, telomere, TRF2, Cytology, QH573-671
Abstract: Linear unconstrained DNA cannot harbor supercoils since these supercoils can diffuse and be eliminated by free rotation of the DNA strands at the end of the molecule. Mammalian telomeres, despite constituting the ends of linear chromosomes, can hold supercoils and be subjected to topological stress. While negative supercoiling was previously observed, thus proving the existence of telomeric topological constraints, positive supercoils were never probed due to the lack of an appropriate tool. Indeed, the few tools available currently could only investigate unwound (Trioxsalen) or overwound (GapR) DNA topology (variations in twist) but not the variations in writhe (supercoils and plectonemes). To address this question, we have designed innovative tools aimed at analyzing both positive and negative DNA writhe in cells. Using them, we could observe the build-up of positive supercoils following replication stress and inhibition of Topoisomerase 2 on telomeres. TRF2 depletion caused both telomere relaxation and an increase in positive supercoils while the inhibition of Histone Deacetylase I and II by TSA only caused telomere relaxation. Moving outside telomeres, we also observed a build-up of positive supercoils on the FRA3B fragile site following replication stress, suggesting a topological model of DNA fragility for this site.
Published: 2024
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2. Telomere DNA length regulation is influenced by seasonal temperature differences in short-lived but not in long-lived reef-building corals

Author: Alice Rouan, Melanie Pousse, Nadir Djerbi, Barbara Porro, Guillaume Bourdin, Quentin Carradec, Benjamin CC. Hume, Julie Poulain, Julie Lê-Hoang, Eric Armstrong, Sylvain Agostini, Guillem Salazar, Hans-Joachim Ruscheweyh, Jean-Marc Aury, David A. Paz-García, Ryan McMinds, Marie-Josèphe Giraud-Panis, Romane Deshuraud, Alexandre Ottaviani, Lycia Die Morini, Camille Leone, Lia Wurzer, Jessica Tran, Didier Zoccola, Alexis Pey, Clémentine Moulin, Emilie Boissin, Guillaume Iwankow, Sarah Romac, Colomban de Vargas, Bernard Banaigs, Emmanuel Boss, Chris Bowler, Eric Douville, Michel Flores, Stéphanie Reynaud, Olivier P. Thomas, Romain Troublé, Rebecca Vega Thurber, Serge Planes, Denis Allemand, Stephane Pesant, Pierre E. Galand, Patrick Wincker, Shinichi Sunagawa, Eric Röttinger, Paola Furla, Christian R. Voolstra, Didier Forcioli, Fabien Lombard, and Eric Gilson
Subjects: Science
Abstract: Abstract Telomeres are environment-sensitive regulators of health and aging. Here,we present telomere DNA length analysis of two reef-building coral genera revealing that the long- and short-term water thermal regime is a key driver of between-colony variation across the Pacific Ocean. Notably, there are differences between the two studied genera. The telomere DNA lengths of the short-lived, more stress-sensitive Pocillopora spp. colonies were largely determined by seasonal temperature variation, whereas those of the long-lived, more stress-resistant Porites spp. colonies were insensitive to seasonal patterns, but rather influenced by past thermal anomalies. These results reveal marked differences in telomere DNA length regulation between two evolutionary distant coral genera exhibiting specific life-history traits. We propose that environmentally regulated mechanisms of telomere maintenance are linked to organismal performances, a matter of paramount importance considering the effects of climate change on health.
Published: 2023
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3. Multifunctionality of the Telomere-Capping Shelterin Complex Explained by Variations in Its Protein Composition

Author: Claire Ghilain, Eric Gilson, and Marie-Josèphe Giraud-Panis
Subjects: telomere, aging, Shelterin, senescence, DNA damage response, Cytology, QH573-671
Abstract: Protecting telomere from the DNA damage response is essential to avoid the entry into cellular senescence and organismal aging. The progressive telomere DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. In several organisms, including mammals, telomeres are protected by a protein complex named Shelterin that counteract at various levels the DNA damage response at chromosome ends through the specific function of each of its subunits. The changes in Shelterin structure and function during development and aging is thus an intense area of research. Here, we review our knowledge on the existence of several Shelterin subcomplexes and the functional independence between them. This leads us to discuss the possibility that the multifunctionality of the Shelterin complex is determined by the formation of different subcomplexes whose composition may change during aging.
Published: 2021
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4. Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones

Author: Melania D’Angiolo, Jia-Xing Yue, Matteo De Chiara, Benjamin P. Barré, Marie-Josèphe Giraud Panis, Eric Gilson, and Gianni Liti
Subjects: Genetics
Abstract: Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1000 S. cerevisiae strains enabled us to explore telomere DNA length variation at an unprecedented scale. Here, we developed a bioinformatic pipeline (YeaISTY) to estimate telomere DNA length from whole-genome-sequences and applied it to the sequenced 1011 S. cerevisiae collection. Our results revealed broad natural telomere DNA length variation among the isolates. Notably, telomere DNA length is shorter in those derived from wild rather than domesticated environments. Wild isolates are enriched in loss-of-function mutations in genes known to regulate telomere DNA length and the return of domesticated yeasts to a wild habitat coincides with shorter telomeres. Moreover, telomere DNA length variation is associated with mitochondrial metabolism, and this association is driven by wild strains. Overall, these findings suggest that budding yeasts’ telomere DNA length regulation might be shaped by ecological life-styles.
Published: 2022
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5. The Telomeric Protein TRF2 Regulates Angiogenesis by Binding and Activating the PDGFRβ Promoter

Author: Mounir El Maï, Kay-Dietrich Wagner, Jean-François Michiels, Damien Ambrosetti, Arnaud Borderie, Sandrine Destree, Valerie Renault, Nadir Djerbi, Marie-Josèphe Giraud-Panis, Eric Gilson, and Nicole Wagner
Subjects: Biology (General), QH301-705.5
Abstract: Telomeric repeat binding factor 2 (TRF2), which plays a central role in telomere capping, is frequently increased in human tumors. We reveal here that TRF2 is expressed in the vasculature of most human cancer types, where it colocalizes with the Wilms’ tumor suppressor WT1. We further show that TRF2 is a transcriptional target of WT1 and is required for proliferation, migration, and tube formation of endothelial cells. These angiogenic effects of TRF2 are uncoupled from its function in telomere capping. Instead, TRF2 binds and transactivates the promoter of the angiogenic tyrosine kinase platelet-derived growth factor receptor β (PDGFRβ). These findings reveal an unexpected role of TRF2 in neoangiogenesis and delineate a distinct function of TRF2 as a transcriptional regulator.
Published: 2014
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6. Human RAP 1 specifically protects telomeres of senescent cells from DNA damage

Author: Marie-Josèphe Giraud-Panis, Jia-Xing Yue, Liudmyla Lototska, Nicola J. Royle, Jing Li, Jing Ye, Zhou Songyang, Aaron Mendez-Bermudez, Gianni Liti, Eric Gilson, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: DNA Replication, Telomerase, endocrine system, DNA damage, telomeres Subject Categories Autophagy & Cell Death, Telomere Capping, [SDV]Life Sciences [q-bio], Telomere-Binding Proteins, Biology, Biochemistry, non-homologous end joining, 03 medical and health sciences, replicative senescence, 0302 clinical medicine, Report, Genetics, chromosome fusions, Animals, Humans, Molecular Biology, Cellular Senescence, Recombination & Repair, 030304 developmental biology, 0303 health sciences, RAP1, DNA replication, DNA Replication, Repair & Recombination, Telomere, telomeres, Cell biology, Non-homologous end joining, Transcription Factor AP-1, enzymes and coenzymes (carbohydrates), non‐homologous end joining, Rap1, Autophagy & Cell Death, Homologous recombination, 030217 neurology & neurosurgery, DNA Damage, HeLa Cells, Reports
Abstract: Repressor/activator protein 1 (RAP1) is a highly evolutionarily conserved protein found at telomeres. Although yeast Rap1 is a key telomere capping protein preventing non‐homologous end joining (NHEJ) and consequently telomere fusions, its role at mammalian telomeres in vivo is still controversial. Here, we demonstrate that RAP1 is required to protect telomeres in replicative senescent human cells. Downregulation of RAP1 in these cells, but not in young or dividing pre‐senescent cells, leads to telomere uncapping and fusions. The anti‐fusion effect of RAP1 was further explored in a HeLa cell line where RAP1 expression was depleted through an inducible CRISPR/Cas9 strategy. Depletion of RAP1 in these cells gives rise to telomere fusions only when telomerase is inhibited. We further show that the fusions triggered by RAP1 loss are dependent upon DNA ligase IV. We conclude that human RAP1 is specifically involved in protecting critically short telomeres. This has important implications for the functions of telomeres in senescent cells., Human RAP1 specifically protects critically short telomeres from DNA damage response activation and telomere fusions in replicative senescent fibroblasts and tumor cells upon telomerase inhibition.
Published: 2020
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7. TRF2 controls telomeric nucleosome organization in a cell cycle phase-dependent manner.

Author: Alessandra Galati, Frédérique Magdinier, Valentina Colasanti, Serge Bauwens, Sébastien Pinte, Ruggero Ricordy, Marie-Josèphe Giraud-Panis, Miriam Caroline Pusch, Maria Savino, Stefano Cacchione, and Eric Gilson
Subjects: Medicine, Science
Abstract: Mammalian telomeres stabilize chromosome ends as a result of their assembly into a peculiar form of chromatin comprising a complex of non-histone proteins named shelterin. TRF2, one of the shelterin components, binds to the duplex part of telomeric DNA and is essential to fold the telomeric chromatin into a protective cap. Although most of the human telomeric DNA is organized into tightly spaced nucleosomes, their role in telomere protection and how they interplay with telomere-specific factors in telomere organization is still unclear. In this study we investigated whether TRF2 can regulate nucleosome assembly at telomeres.By means of chromatin immunoprecipitation (ChIP) and Micrococcal Nuclease (MNase) mapping assay, we found that the density of telomeric nucleosomes in human cells was inversely proportional to the dosage of TRF2 at telomeres. This effect was not observed in the G1 phase of the cell cycle but appeared coincident of late or post-replicative events. Moreover, we showed that TRF2 overexpression altered nucleosome spacing at telomeres increasing internucleosomal distance. By means of an in vitro nucleosome assembly system containing purified histones and remodeling factors, we reproduced the short nucleosome spacing found in telomeric chromatin. Importantly, when in vitro assembly was performed in the presence of purified TRF2, nucleosome spacing on a telomeric DNA template increased, in agreement with in vivo MNase mapping.Our results demonstrate that TRF2 negatively regulates the number of nucleosomes at human telomeres by a cell cycle-dependent mechanism that alters internucleosomal distance. These findings raise the intriguing possibility that telomere protection is mediated, at least in part, by the TRF2-dependent regulation of nucleosome organization.
Published: 2012
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8. Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2

Author: Michael Schertzer, Arturo Londoño-Vallejo, Aaron Mendez-Bermudez, Michelle Debatisse, Mylène Perderiset, Karine Jamet, Geneviève Almouzni, Jing Ye, Nicolas Nottet, Eric Gilson, Stephane Koundrioukoff, Marie Josèphe Giraud-Panis, Macarena Mowinckel, Liudmyla Lototska, Agurtzane Irizar, Olivier Croce, Serge Bauwens, Mare Paule Teulade-Fichou, International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de biologie moléculaire et cellulaire, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Institut Sophia Agrobiotech (ISA), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA), Dynamique nucléaire et plasticité du génome (DNPG), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Telomeres and Cancer Laboratory (Lab ellis e Ligue), Telomeres and Cancer Laboratory, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Géosciences Environnement Toulouse (GET), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Sophia Agrobiotech [Sophia Antipolis] (ISA), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Dynamique du noyau, Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), School of Mechanical Engineering, Sungkyunkwan University [Suwon] (SKKU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Institut Curie, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, biology, Heterochromatin, Telomere Capping, [SDV]Life Sciences [q-bio], Helicase, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, Chromosome Fragility, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Shelterin, 3. Good health, Chromatin, Cell biology, Telomere, 03 medical and health sciences, 030104 developmental biology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Centromere, biology.protein, Molecular Biology, ComputingMilieux_MISCELLANEOUS
Abstract: Summary Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin. In a process involving its N-terminal basic domain, TRF2 binds to pericentromeric Satellite III sequences during S phase, allowing the recruitment of the G-quadruplex-resolving helicase RTEL1 to facilitate fork progression. We also show that TRF2 is required for the stability of other heterochromatic regions localized throughout the genome, paving the way for future research on heterochromatic replication and its relationship with aging and cancer.
Published: 2018
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9. Dynamics under the Telomeric Bridge

Author: Sabrina Pisano, Eric Gilson, Marie-Josèphe Giraud-Panis, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Allosteric regulation, Telomere-Binding Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Shelterin Complex, 03 medical and health sciences, Telomere Homeostasis, Schizosaccharomyces, Humans, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Telomere-binding protein, Genetics, biology, Cell Biology, Telomere, biology.organism_classification, Shelterin, 3. Good health, Cell biology, 030104 developmental biology, Schizosaccharomyces pombe
Abstract: In this issue of Molecular Cell, Kim et al. (2017) have studied the structure and organization of the shelterin protein complex protecting telomeres in Schizosaccharomyces pombe and humans and discovered an allosteric structural transition that drives the formation of the shelterin complex and participates in telomere length regulation.
Published: 2017
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10. TRF2 and Apollo Cooperate with Topoisomerase 2α to Protect Human Telomeres from Replicative Damage

Author: Annamaria Biroccio, Eric Gilson, Anaïs Poulet, Christelle Lenain, Anna Bizard, Delphine Benarroch, Arturo Londoño-Vallejo, Erica Salvati, Laure Sabatier, Els Verhoeyen, Julia Morere, Jing Ye, Sébastien Britton, Bernard Salles, Yunlin Wu, Angela Maria Rizzo, Marc Nadal, Patrick Calsou, Adelaïde Saint-Léger, Marie Josèphe Giraud-Panis, Frédérique Magdinier, Simon Amiard, Serge Bauwens, Shanghai Jiao Tong University School of Medicine, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et pathologie des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Laboratoire Joliot Curie, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Radiobiologie et d'Oncologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Medical Genetics, Centre Hospitalier Universitaire de Nice (CHU Nice), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratory of Biology and Pathology of Genomes, Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: [SDV]Life Sciences [q-bio], MESH: Antigens, Neoplasm, MESH: DNA Replication, chemistry.chemical_compound, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Telomeric Repeat Binding Protein 2, ComputingMilieux_MISCELLANEOUS, Cellular Senescence, Genetics, Telomere-binding protein, 0303 health sciences, Nuclear Proteins, MESH: Telomeric Repeat Binding Protein 2, Telomere, DNA-Binding Proteins, MESH: DNA Repair Enzymes, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Cell Aging, 030220 oncology & carcinogenesis, DNA supercoil, Cell aging, DNA Replication, DNA damage, DNA repair, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Antigens, Neoplasm, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: DNA Topoisomerases, Type II, Eukaryotic, MESH: DNA Damage, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), DNA replication, DNA, Protein Structure, Tertiary, DNA Repair Enzymes, DNA Topoisomerases, Type II, Exodeoxyribonucleases, chemistry, MESH: Telomere, MESH: Nuclear Proteins, MESH: DNA-Binding Proteins, DNA Damage
Abstract: International audience; Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2 regulates the 5' exonuclease activity of its binding partner, Apollo, a member of the metallo-beta-lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome ends. Genetic data indicate that DNA topoisomerase 2alpha acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1, TOP2alpha, and TOP2beta at telomeres. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres.
Published: 2010
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11. TRF2/RAP1 and DNA–PK mediate a double protection against joining at telomeric ends

Author: Eric Gilson, Philippe Frit, Marie-Josèphe Giraud-Panis, Oriane Bombarde, Céline Boby, Bernard Salles, Dennis Gomez, and Patrick Calsou
Subjects: Genome instability, DNA Ligases, DNA Repair, DNA repair, Telomere-Binding Proteins, DNA-Activated Protein Kinase, LIG4, Biology, Article, Genomic Instability, Shelterin Complex, General Biochemistry, Genetics and Molecular Biology, DNA Ligase ATP, Humans, Telomeric Repeat Binding Protein 2, Molecular Biology, chemistry.chemical_classification, Telomere-binding protein, DNA ligase, General Immunology and Microbiology, General Neuroscience, fungi, DNA, Telomere, Molecular biology, Non-homologous end joining, enzymes and coenzymes (carbohydrates), chemistry, embryonic structures, Rap1, HeLa Cells
Abstract: DNA-dependent protein kinase (DNA-PK) is a double-strand breaks repair complex, the subunits of which (KU and DNA-PKcs) are paradoxically present at mammalian telomeres. Telomere fusion has been reported in cells lacking these proteins, raising two questions: how is DNA-PK prevented from initiating classical ligase IV (LIG4)-dependent non-homologous end-joining (C-NHEJ) at telomeres and how is the backup end-joining (EJ) activity (B-NHEJ) that operates at telomeres under conditions of C-NHEJ deficiency controlled? To address these questions, we have investigated EJ using plasmid substrates bearing double-stranded telomeric tracks and human cell extracts with variable C-NHEJ or B-NHEJ activity. We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA-PK end binding and activation step and (2) DNA-PK counteracts a potent LIG4-independent EJ mechanism. Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells.
Published: 2010
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12. TRF2-Mediated Control of Telomere DNA Topology as a Mechanism for Chromosome-End Protection

Author: Marie-Hélène Le Du, Simona Miron, Bei Pei, Hong Wang, Eric Gilson, Parminder Kaur, Arturo Londoño-Vallejo, Jing Ye, Emilie Jaune, Aaron Mendez-Bermudez, Sabrina Pisano, Marie-Josèphe Giraud-Panis, Vincent Fraisier, Julien Cherfils-Vicini, Nadir Djerbi, Eric Aeby, Delphine Benarroch-Popivker, Serge Bauwens, Kevin Foucher, Chrysa M Latrick, Liudmyla Lototska, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), International Laboratory in Hematology and Cancer, Shanghai Jiao Tong University School of Medicine, Physics Department, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Swiss Institute for Experimental Cancer Research - Lausanne (ISREC), Swiss Institute for Experimental Cancer Research, Enveloppe Nucléaire, Télomères et Réparation de l’ADN (INTGEN), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), ANR-10-BLAN-1512,TELOLOOP,Rôle de la protéine TRF2 et de ses partenaires dans la formation et la stabilité de la t-loop des télomères humains(2010), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Institut de Recherche sur le Cancer et le Vieillissement ( IRCAN ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), North Carolina State University [Raleigh] ( NCSU ), Compartimentation et dynamique cellulaires ( CDC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ), Swiss Institute for Experimental Cancer Research - Lausanne ( ISREC ), Enveloppe Nucléaire, Télomères et Réparation de l’ADN ( INTGEN ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Dynamique de l'information génétique : bases fondamentales et cancer ( DIG CANCER ), CHU Nice, ANR-1582-30020690,TELOLOOP,ANR-1582-30020690, ANR : LABEX SIGNALIFE,ANR-11-LABX-0028-01, Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Telomeres and Cancer Laboratory, Institut Curie [Paris], School of Mechanical Engineering, Sungkyunkwan University [Suwon] (SKKU), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: Models, Molecular, 0301 basic medicine, DNA End-Joining Repair, [SDV]Life Sciences [q-bio], Ataxia Telangiectasia Mutated Proteins, TRF2, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, Shelterin Complex, chemistry.chemical_compound, Telomeric Repeat Binding Protein 2, Base Pairing, ComputingMilieux_MISCELLANEOUS, Telomere-binding protein, Mutation, telomere, RAP1, DNA topology, DNA wrapping, Signal Transduction, DNA damage, Base pair, Telomere-Binding Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Topology, Article, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, [ SDV ] Life Sciences [q-bio], Lysine, DNA, Cell Biology, Shelterin, Molecular biology, Protein Structure, Tertiary, Telomere, enzymes and coenzymes (carbohydrates), 030104 developmental biology, chemistry, Nucleic Acid Conformation, DNA Damage, HeLa Cells
Abstract: International audience; The shelterin proteins protect telomeres against activation of the DNA damage checkpoints and recombinational repair. We show here that a dimer of the shelterin subunit TRF2 wraps ∼ 90 bp of DNA through several lysine and arginine residues localized around its homodimerization domain. The expression of a wrapping-deficient TRF2 mutant, named Top-less, alters telomeric DNA topology, decreases the number of terminal loops (t-loops), and triggers the ATM checkpoint, while still protecting telomeres against non-homologous end joining (NHEJ). In Top-less cells, the protection against NHEJ is alleviated if the expression of the TRF2-interacting protein RAP1 is reduced. We conclude that a distinctive topological state of telomeric DNA, controlled by the TRF2-dependent DNA wrapping and linked to t-loop formation, inhibits both ATM activation and NHEJ. The presence of RAP1 at telomeres appears as a backup mechanism to prevent NHEJ when topology-mediated telomere protection is impaired.
Published: 2016
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13. Cisplatin Is a DNA-Damaging Antitumour Compound Triggering Multifactorial Biochemical Responses in Cancer Cells: Importance of Apoptotic Pathways

Author: Marie-Josèphe Giraud-Panis, Jean-Marc Malinge, and Yuliya Sedletska
Subjects: Cancer Research, Programmed cell death, DNA damage, Antineoplastic Agents, Apoptosis, Biology, Pharmacology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Neoplasms, medicine, Animals, Humans, 030304 developmental biology, Cisplatin, 0303 health sciences, 3. Good health, Telomere, chemistry, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Molecular Medicine, DNA mismatch repair, DNA, DNA Damage, medicine.drug
Abstract: cis-diamminedichloroplatinum(II) (cisplatin) is among the most active antitumour agent used in human chemotherapy. The purpose of this review is to give an insight in several molecular mechanisms that mediate the sensitivity of cancer cells to this drug and to show how recent progress in our knowledge on some critical molecular events should lay the foundations of a more rational approach to anticancer drug design. Cisplatin is primarily considered as a DNA-damaging anticancer drug, mainly forming different types of bifunctional adducts in its reaction with cellular DNA. We will address the question of cellular activity disruption that cisplatin could cause through binding to more sensitive region of the genome such as telomeres. Cellular mechanisms of resistance to cisplatin are multifactorial and contribute to severe limitation in the use of this drug in clinics. They include molecular events modulating the amount of drug-DNA interaction, such as a reduction in cisplatin accumulation inside cancer cells or inactivation of cisplatin by thiol-containing species. Other important mechanisms acting downstream to the initial reaction of cisplatin with DNA, include an increase in adducts repair and a decrease in induction of apoptosis. Recently accumulating evidence suggest a role of the long patch DNA mismatch repair system in sensing cisplatin-damaged DNA and in triggering cell death through a c-Abl- and p73-dependent cascade; two other important pathways have been unravelled that are the mitogen-activated protein kinase cascade and the tumor suppressor p53. Several of these mechanisms underlying cisplatin resistance have been exploited to design new platinum derivatives. This issue will be covered in the present review.
Published: 2005
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14. The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres

Author: Arturo Londoño-Vallejo, Nadir Djerbi, Marie-Josèphe Giraud-Panis, Eric Gilson, Fiorentina Ascenzioni, Adélaïde Saint-Léger, Melanie Koelblen, Amadou Bah, Livia Civitelli, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: Tn3 transposon, [SDV]Life Sciences [q-bio], Transfection, Recombinases, 03 medical and health sciences, Endonuclease, 0302 clinical medicine, Telomere Homeostasis, Report, Recombinase, Humans, Telomeric Repeat Binding Protein 2, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Recombination, Genetic, Genetics, 0303 health sciences, biology, Holliday Junction Resolvases, Cell Biology, Telomere, Endonucleases, Shelterin, MUS81, Cell biology, DNA-Binding Proteins, HEK293 Cells, 030220 oncology & carcinogenesis, biology.protein, trf2, shelterin, recombination, telomere, Tumor Suppressor Protein p53, Homologous recombination, Plasmids, Developmental Biology
Abstract: The stability of mammalian telomeres depends upon TRF2, which prevents inappropriate repair and checkpoint activation. By using a plasmid integration assay in yeasts carrying humanized telomeres, we demonstrated that TRF2 possesses the intrinsic property to both stimulate initial homologous recombination events and to prevent their resolution via its basic N-terminal domain. In human cells, we further showed that this TRF2 domain prevents telomere shortening mediated by the resolvase-associated protein SLX4 as well as GEN1 and MUS81, 2 different types of endonucleases with resolvase activities. We propose that various types of resolvase activities are kept in check by the basic N-terminal domain of TRF2 in order to favor an accurate repair of the stalled forks that occur during telomere replication.
Published: 2014
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15. Replacement of an NH3by an Iminoether in Transplatin Makes an Antitumor Drug from an Inactive Compound

Author: Daniel Locker, Angelina Boccarelli, Mauro Coluccia, Francesco P. Intini, Marc Leng, Annie Schwartz, Giovanni Natile, Marie-Josèphe Giraud-Panis, Domenico Giordano, and Claudio Pisano
Subjects: Stereochemistry, Guanine, DNA Footprinting, Oligonucleotides, Antineoplastic Agents, Adduct, DNA Adducts, Mice, chemistry.chemical_compound, In vivo, Tumor Cells, Cultured, medicine, Animals, Humans, Pharmacology, Cisplatin, Leukemia P388, Chemistry, High Mobility Group Proteins, Thiourea, DNA, DNA Restriction Enzymes, DNA-Directed RNA Polymerases, Rats, Disease Models, Animal, Cross-Linking Reagents, Naked DNA, Nucleic Acid Conformation, Molecular Medicine, Drug Screening Assays, Antitumor, Cytosine, medicine.drug
Abstract: To investigate the modifications of antitumor activity and DNA binding mode of transplatin after replacement of one nonleaving group NH(3) by an iminoether group, trans-[PtCl(2)(Z-HN=C(OMe)Me)(NH(3)] and trans-[PtCl(2)(E-HN=C(OMe)Me)(NH(3)] complexes (differing in the Z or E configuration of iminoether, and abbreviated mixed Z and mixed E, respectively), have been synthesized. In a panel of human tumor cell lines, both mixed Z and mixed E show a cytotoxic potency higher than that of transplatin, the mean IC(50) values being 103, 37, and 215 microM, respectively. In vivo mixed Z is more active and less toxic than mixed E in murine P388 leukemia and retains its efficacy against SK-OV-3 human cancer cell xenograft in nude mice. In the reaction with naked DNA, mixed Z forms monofunctional adducts that do not evolve into intrastrand cross-links but close slowly into interstrand cross-links between complementary guanine and cytosine residues. The monofunctional mixed Z adducts are removed by thiourea and glutathione. The interstrand cross-links behave as hinge joints, increasing the flexibility of DNA double helix. The mixed Z, transplatin, and cisplatin interstrand cross-links, as well as mixed Z monofunctional adducts are not specifically recognized by HMG1 protein, which was confirmed to be able to specifically recognize cisplatin d(GpG) intrastrand cross-links. These data demonstrate that the DNA interaction properties of the antitumor-active mixed Z are very similar to those of transplatin, thus suggesting that clinical inactivity of transplatin could not depend upon its peculiar DNA binding mode.
Published: 2000
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16. Structural recognition and distortion by the DNA junction-resolving enzyme RusA

Author: Marie-Josèphe Giraud-Panis and David M.J. Lilley
Subjects: Protein Conformation, Recombinant Fusion Proteins, Gene Expression, Cleavage (embryo), Catalysis, Substrate Specificity, Structure-Activity Relationship, chemistry.chemical_compound, Structural Biology, Holliday junction, Protein–DNA interaction, Molecular Biology, Magnesium ion, Rusa, Gel electrophoresis, Endodeoxyribonucleases, biology, Escherichia coli Proteins, Holliday Junction Resolvases, biology.organism_classification, Branch migration, Oligodeoxyribonucleotides, Biochemistry, chemistry, Biophysics, Nucleic Acid Conformation, DNA
Abstract: RusA is a relatively small DNA junction-resolving enzyme of lambdoid phage-origin. Many of the physical characteristics of this enzyme are similar to those of junction-resolving enzymes of different origins. RusA binds to DNA junctions as a dimer, with a dissociation constant of 2 to 7 nM. RusA also exists in dimeric form in free solution, with a half time for subunit exchange of 4.2 minutes. We find that RusA can cleave both fixed junctions and those that can undergo a number of steps of branch migration, and confirm that the enzyme exhibits a strong preference for cleavage 5′ to a CpC sequence. We have isolated a mutant protein, RusA D70N, that is completely inactive in cleavage while binding normally to DNA junctions, suggesting a role for aspartate 70 in the cleavage reaction. Constraining the conformation of the junction by means of tethering the helical ends leads to a marked reduction in cleavage rate by RusA, suggesting that the structure must be altered for cleavage. Using comparative gel electrophoresis we find that the global structure of the DNA junction is altered on RusA binding, into a structure that is different from any that is formed by the free junction. Moreover, the structure of the complex is the same irrespective of the presence or absence of magnesium ions. Thus, like all the junction-resolving enzymes, RusA both recognises and distorts the structure of DNA junctions.
Published: 1998
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17. Nucleic acid structure and recognition

Author: David M.J. Lilley, Derek R. Duckett, Marie-Josèphe Giraud-Panis, Gurminder S. Bassi, Alastair I.H. Murchie, and Robert M. Clegg
Subjects: Hammerhead ribozyme, Xeno nucleic acid, biology, Chemistry, Stereochemistry, Organic Chemistry, Biophysics, biology.organism_classification, Biochemistry, Nucleic acid thermodynamics, chemistry.chemical_compound, Nucleic acid, Nucleic acid structure, Hairpin ribozyme, Nucleic acid analogue, DNA
Abstract: We review the global structures adopted by branched nucleic acids, including three- and four-way helical junctions in DNA and RNA. We find that some general folding principles emerge. First, all the structures exhibit a tendency to undergo pairwise coaxial helical stacking when permitted by the local stereochemistry of strand exchange. Second, metal ions generally play an important role in facilitating folding of branched nucleic acids. These principles can be applied to functionally important branched nucleic acids, such as the Holliday DNA junction of genetic recombination, and the hammerhead ribozyme in RNA.
Published: 1997
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18. Recognition and manipulation of branched DNA structure by junction-resolving enzymes 1 1Edited by P. E. Wright

Author: Marie-Josèphe Giraud-Panis, Malcolm F. White, J. Richard G. Pöhler, and David M.J. Lilley
Subjects: chemistry.chemical_classification, Mutant, Biology, Cleavage (embryo), law.invention, DNA binding site, chemistry.chemical_compound, Molecular recognition, Enzyme, chemistry, Biochemistry, Structural Biology, law, Recombinant DNA, Protein–DNA interaction, Molecular Biology, DNA
Abstract: The junction-resolving enzymes are a class of nucleases that introduce paired cleavages into four-way DNA junctions. They are important in DNA recombination and repair, and are found throughout nature, from eubacteria and their bacteriophages through to higher eukaryotes and their viruses. These enzymes exhibit structure-selective binding to DNA junctions; although cleavage may be more or less sequence-dependent, binding affinity is purely related to the branched structure of the DNA. Binding and cleavage events can be separated for a number of the enzymes by mutagenesis, and mutant proteins that are defective in cleavage while retaining normal junction-selective binding have been isolated. Critical acidic residues have been identified in several resolving enzymes, suggesting a role in the coordination of metal ions that probably deliver the hydrolytic water molecule. The resolving enzymes all bind to junctions in dimeric form, and the subunits introduce independent cleavages within the lifetime of the enzyme-junction complex to ensure resolution of the four-way junction. In addition to recognising the structure of the junction, recent data from four different junction-resolving enzymes indicate that they also manipulate the global structure. In some cases this results in severe distortion of the folded structure of the junction. Understanding the recognition and manipulation of DNA structure by these enzymes is a fascinating challenge in molecular recognition.
Published: 1997
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19. Near-simultaneous DNA cleavage by the subunits of the junction-resolving enzyme T4 endonuclease VII

Author: David M.J. Lilley and Marie-Josèphe Giraud-Panis
Subjects: Stereochemistry, Dimer, Mutant, Biology, Cleavage (embryo), General Biochemistry, Genetics and Molecular Biology, Structure-Activity Relationship, chemistry.chemical_compound, Holliday junction, Bacteriophage T4, Protein–DNA interaction, Molecular Biology, Recombination, Genetic, Endodeoxyribonucleases, General Immunology and Microbiology, DNA, Superhelical, General Neuroscience, Genetic Complementation Test, DNA-Binding Proteins, chemistry, Cruciform, Biochemistry, Mutation, Nucleic Acid Conformation, DNA supercoil, Dimerization, DNA, Research Article, Plasmids
Abstract: In common with a number of other DNA junction-resolving enzymes, endonuclease VII of bacteriophage T4 binds to a four-way DNA junction as a dimer, and cleaves two strands of the junction. We have used a supercoil-stabilized cruciform substrate to probe the simultaneity of cleavage at the two sites. Active endonuclease VII converts the supercoiled circular DNA directly into linear product, indicating that the two cleavage reactions must occur within the lifetime of the protein-junction complex. By contrast, a heterodimer of active enzyme and an inactive mutant endonuclease VII leads to the formation of nicked circular product, showing that the subunits operate fully independently.
Published: 1997
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20. Effect of Rap1 binding on DNA distortion and potassium permanganate hypersensitivity

Author: Eric Gilson, Marie-Josèphe Giraud-Panis, Simona Miron, Eric Le Cam, Olivier Piétrement, Bianca Sclavi, B. Matot, Yann-Vaï Le Bihan, Marie-Hélène Le Du, Sylvaine Gasparini, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Structurale et Radiobiologie (LBSR), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Imagerie intégrative de la molécule à l'organisme, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Bioénergétique, Biologie Stucturale, et Mécanismes (SB2SM), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Le Cam, Eric, Université Nice Sophia Antipolis (... - 2019) (UNS), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: endocrine system, Saccharomyces cerevisiae Proteins, [SDV]Life Sciences [q-bio], Telomere-Binding Proteins, Mutant, Saccharomyces cerevisiae, Arginine, Crystallography, X-Ray, Shelterin Complex, Cytosine, 03 medical and health sciences, chemistry.chemical_compound, Nucleic acid thermodynamics, 0302 clinical medicine, Potassium Permanganate, Structural Biology, Binding site, DNA, Fungal, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, Permanganate, Hydrogen Bonding, General Medicine, biology.organism_classification, Solutions, [SDV] Life Sciences [q-bio], enzymes and coenzymes (carbohydrates), Potassium permanganate, chemistry, Biochemistry, Biophysics, Nucleic Acid Conformation, 030217 neurology & neurosurgery, DNA, Protein Binding, Transcription Factors
Abstract: Repressor activator protein 1 (Rap1) is an essential factor involved in transcription and telomere stability in the budding yeast Saccharomyces cerevisiae. Its interaction with DNA causes hypersensitivity to potassium permanganate, suggesting local DNA melting and/or distortion. In this study, various Rap1-DNA crystal forms were obtained using specifically designed crystal screens. Analysis of the DNA conformation showed that its distortion was not sufficient to explain the permanganate reactivity. However, anomalous data collected at the Mn edge using a Rap1-DNA crystal soaked in potassium permanganate solution indicated that the DNA conformation in the crystal was compatible with interaction with permanganate ions. Sequence-conservation analysis revealed that double-Myb-containing Rap1 proteins all carry a fully conserved Arg580 at a position that may favour interaction with permanganate ions, although it is not involved in the hypersensitive cytosine distortion. Permanganate reactivity assays with wild-type Rap1 and the Rap1[R580A] mutant demonstrated that Arg580 is essential for hypersensitivity. AFM experiments showed that wild-type Rap1 and the Rap1[R580A] mutant interact with DNA over 16 successive binding sites, leading to local DNA stiffening but not to accumulation of the observed local distortion. Therefore, Rap1 may cause permanganate hypersensitivity of DNA by forming a pocket between the reactive cytosine and Arg580, driving the permanganate ion towards the C5-C6 bond of the cytosine.
Published: 2013
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21. T4 Endonuclease VII

Author: David M.J. Lilley and Marie-Josèphe Giraud-Panis
Subjects: chemistry.chemical_classification, Cell Biology, Biochemistry, Amino acid, chemistry.chemical_compound, Protein structure, chemistry, Aspartic acid, Metalloprotein, Binding site, Molecular Biology, Peptide sequence, Histidine, DNA
Abstract: The DNA junction-resolving enzyme endonuclease VII of bacteriophage T4 contains a zinc-binding region toward the N-terminal end of the primary sequence. In the center of this 39-amino acid section (between residues 38 and 44) lies the sequence HLDHDHE, termed the His-acid cluster. Closely related sequences are found in three other proteins that have similar zinc-binding motifs. We have analyzed the function of these residues by a site-directed mutagenesis approach, modifying single amino acids and studying the properties of the resulting N-terminal protein A fusions. No sequence changes within the His-acid cluster led to a change in zinc content of the protein, indicating that these residues are not involved in the coordination of zinc. We found that the N-terminal aspartate residue (Asp-40) and the two histidine residues (His-41 and His-43) within the cluster are essential for junction-cleavage activity of the proteins. However, all sequence variations within this region generate proteins that retain their ability to bind to four-way DNA junctions (with minor changes in binding affinity in some cases) and to distort their global structure in the same manner as active enzymes. We conclude that the process of cleavage can be uncoupled from those of binding to and distortion of the junction. It is probable that some amino acid side chains of the His-acid cluster participate in the phosphodiester cleavage mechanism of endonuclease VII. The essential aspartate residue might be required for coordination of catalytic metal ions.
Published: 1996
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22. T4 Endonuclease VII Selects and Alters the Structure of the Four-way DNA Junction; Binding of a Resolution-defective Mutant Enzyme

Author: David M.J. Lilley, Marie-Josèphe Giraud-Panis, and Richard G.J. Pöhler
Subjects: Models, Molecular, HMG-box, Protein Conformation, Recombinant Fusion Proteins, Molecular Sequence Data, Biology, chemistry.chemical_compound, Protein structure, Structural Biology, Mutant protein, Holliday junction, Amino Acid Sequence, Cloning, Molecular, Binding site, Staphylococcal Protein A, Molecular Biology, Replication protein A, Nuclease, Binding Sites, Endodeoxyribonucleases, Base Sequence, DNA, Zinc, chemistry, Biochemistry, Factor Xa, Mutagenesis, Site-Directed, Biophysics, biology.protein, Nucleic Acid Conformation, Electrophoresis, Polyacrylamide Gel, Protein Binding
Abstract: Bacteriophage T4 endonuclease VII is a nuclease that is selective for four-way DNA junctions and related branched DNA species. Using site-directed mutagenesis we have isolated a mutant protein (E86A) that is inactive in the cleavage of DNA junctions while retaining full selectivity of binding. Using endonuclease VII E86A we have shown: (1) The protein binds as a dimer to DNA junctions, with rapid exchange of subunits in free solution. (2) Binding to junctions is highly selective for the structure of DNA junctions; the complex is not displaced by a 1000-fold excess of duplex competitor DNA. (3) On binding endonuclease VII E86A to junctions, the configuration of the helical arms is significantly altered to a structure that is independent of the presence or absence of metal ions. We suggest a model for the structure of the junction in the protein complex. (4) The protein can bind to the junction in two stereochemically equivalent ways, depending upon the sequence of the junction. T4 endonuclease VII is a junction-selective enzyme that both recognises and manipulates the structure of its substrate.
Published: 1996
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23. Biotin-end-functionalized highly fluorescent water-soluble polymers

Author: José Paulo S. Farinha, Franck D'Agosto, Marie-Josèphe Giraud-Panis, Arnaud Favier, Paula Relogio, Mariana Beija, Marie-Thérèse Charreyre, Maël Bathfield, José M. G. Martinho, Zofia Haftek-Terreau, Bernard Mandrand, CQFM, Centro de Química-Física Molecular, IN - Institute of Nanosciences and Nanotechnology, Centro de Química-Física Molecular, Ingénierie des Matériaux Polymères (IMP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie, Catalyse, Polymères et Procédés, R 5265 (C2P2), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Systèmes Macromoléculaires et Physiopathologie Humaine (SMPH), BIOMERIEUX-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)
Subjects: Streptavidin, Polymers and Plastics, PROTEINS, Bioengineering, 02 engineering and technology, 010402 general chemistry, RESONANCE ENERGY-TRANSFER, 01 natural sciences, Biochemistry, chemistry.chemical_compound, Organic chemistry, Reversible addition−fragmentation chain-transfer polymerization, chemistry.chemical_classification, DERIVATIVES, Organic Chemistry, RAFT POLYMERIZATION, LUCIFER YELLOW, Chain transfer, Polymer, [CHIM.MATE]Chemical Sciences/Material chemistry, 021001 nanoscience & nanotechnology, Fluorescence, Combinatorial chemistry, Photobleaching, 0104 chemical sciences, EXCITED-STATE DYNAMICS, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Biotinylation, CELLS, STREPTAVIDIN, MEMBRANE, 0210 nano-technology, Biosensor, CONJUGATED POLYMERS
Abstract: International audience; Many biosensing and imaging systems use fluorescence detection. We present the synthesis of biotin-end-functionalized highly fluorescent water-soluble polymers for potential use in biotin-avidin systems. Statistical polymers of N-acryloylmorpholine (NAM) and N-acryloxysuccinimide (NAS) were prepared by RAFT polymerization using a biotinylated chain transfer agent that ensured 95% end-functionalization of the chains. They were further labeled with a lucifer yellow (LY) dye, yielding 7 to 62 LY fluorophores per polymer chain. The resulting polymers exhibited reduced fluorescence self-quenching, with 7- to 43-fold higher brightness than free LY dye. In addition, they featured low pH sensitivity and very good photobleaching resistance. Moreover, we showed that a more extended polymer conformation was beneficial to the binding of the terminal biotin with streptavidin. This work paves the way for the development of polymers for signal amplification in biosensing assays, labeling of biotin-receptors at cell surfaces in some cancer studies, labeling of antibodies and microscopy imaging purposes.
Published: 2013
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24. One Identity or More for Telomeres?

Author: Sabrina Pisano, Marie-Hélène Le Du, Eric Gilson, Bei Pei, Marie-Josèphe Giraud-Panis, Delphine Benarroch-Popivker, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: Cancer Research, [SDV]Life Sciences [q-bio], capping complexes, Review Article, Computational biology, Biology, lcsh:RC254-282, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Transcription (biology), chromosome, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, 0303 health sciences, Telomere biology, telomeric chromatin organization, RNA, Robustness (evolution), Cell cycle, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, telomeres, Telomere, Nucleoprotein, DNA topology, chemistry, Oncology, 030217 neurology & neurosurgery, DNA
Abstract: A major issue in telomere research is to understand how the integrity of chromosome ends is controlled. The fact that different types of nucleoprotein complexes have been described at the telomeres of different organisms raises the question of whether they have in common a structural identity that explains their role in chromosome protection. We will review here how telomeric nucleoprotein complexes are structured, comparing different organisms and trying to link these structures to telomere biology. It emerges that telomeres are formed by a complex and specific network of interactions between DNA, RNA, and proteins. The fact that these interactions and associated activities are reinforcing each other might help to guarantee the robustness of telomeric functions across the cell cycle and in the event of cellular perturbations. We will also discuss the recent notion that telomeres have evolved specific systems to overcome the DNA topological stress generated during their replication and transcription. This will lead to revisit the way we envisage the functioning of telomeric complexes since the regulation of topology is central to DNA stability, replication, recombination, and transcription as well as to chromosome higher-order organization.
Published: 2013
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25. The Modular Character of a DNA Junction-resolving Enzyme: A Zinc-binding Motif in Bacteriophage T4 Endonuclease VII

Author: David M.J. Lilley, Marie-Josèphe Giraud-Panis, and Derek R. Duckett
Subjects: Recombinant Fusion Proteins, Molecular Sequence Data, Flap structure-specific endonuclease 1, Biology, Deoxyribonuclease (Pyrimidine Dimer), Viral Proteins, Endonuclease, chemistry.chemical_compound, Protein sequencing, Protein structure, Structural Biology, Escherichia coli, Genes, Synthetic, Holliday junction, Bacteriophage T4, Point Mutation, Histidine, A-DNA, Amino Acid Sequence, Cysteine, Molecular Biology, Binding Sites, Endodeoxyribonucleases, Base Sequence, Protein Structure, Tertiary, Kinetics, Zinc, Biochemistry, chemistry, Mutagenesis, Site-Directed, biology.protein, DNA, Protein Binding
Abstract: Bacteriophage T4 endonuclease VII is one of a class of structure-selective enzymes that resolve helical branchpoints in DNA molecules. The sequence of this protein suggests a modular organisation. We have expressed a synthetic gene encoding endonuclease VII, which has been used in a directed mutagenesis exercise, with the aim of understanding the role of different sections of the protein sequence. Towards the N-terminal end of the protein lies a section of polypeptide in which four cysteine residues distributed in a CxxC-CxxC pattern co-ordinate one atom of zinc. The N-terminal section composed of amino acid residues 1 to 65 isolated from the remaining C-terminal section also binds one mole of zinc, suggesting that this region folds autonomously. Mutation shows that the outer cysteine residues are essential for zinc binding, while the inner cysteine residues are partially degenerate in that either one of the two (but not both) can be replaced while retaining some zinc. The activity as a junction-resolving enzyme correlated qualitatively with the presence of the zinc. In the C-terminal part of the protein lies a section that is 48% identical with a sequence found in the DNA repair protein T4 endonuclease V. We can replace the section of T4 endonuclease VII with the corresponding sequence from T4 endonuclease V with no change in the pattern of cleavage on four-way junctions. The evidence supports a modular construction for T4 endonuclease VII.
Published: 1995
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26. TRF2 Controls Telomeric Nucleosome Organization in a Cell Cycle Phase-Dependent Manner

Author: Marie Josèphe Giraud-Panis, Alessandra Galati, Ruggero Ricordy, Miriam Caroline Pusch, Eric Gilson, Sébastien Pinte, Stefano Cacchione, Valentina Colasanti, Maria Savino, Frédérique Magdinier, Serge Bauwens, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Department of Biology and Biotechnology 'Charles Darwin', Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute of Molecular Pathology and Biology [Rome] (IPBM), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Consiglio Nazionale delle Ricerche (CNR), Adolf-Butenandt-Institut, Molekularbiologie, Ludwig-Maximilians-Universität München (LMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), CNR Istituto di Biologia e Patologia Molecolari [Roma] (CNR | IBPM), and National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR)
Subjects: Nucleosome organization, Nucleosome assembly, [SDV]Life Sciences [q-bio], Gene Expression, lcsh:Medicine, Biochemistry, MESH: Cell Cycle Checkpoints, 0302 clinical medicine, Nucleic Acids, Molecular Cell Biology, Telomeric Repeat Binding Protein 2, lcsh:Science, ComputingMilieux_MISCELLANEOUS, MESH: Chromatin Immunoprecipitation, 0303 health sciences, Multidisciplinary, biology, Chromosome Biology, MESH: Telomeric Repeat Binding Protein 2, Genomics, Telomere, Chromatin, Nucleosomes, Cell biology, Telomeres, Histone, 030220 oncology & carcinogenesis, Protein Binding, Research Article, Chromatin Immunoprecipitation, Chromosome Structure and Function, MESH: Cell Line, Tumor, MESH: Gene Expression, Telomere organization, MESH: Chromatin, 03 medical and health sciences, MESH: Nucleosomes, Cell Line, Tumor, DNA-binding proteins, Humans, Nucleosome, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biology, 030304 developmental biology, MESH: Humans, lcsh:R, MESH: Chromatin Assembly and Disassembly, cell cycle, chromatin, nucleosome, telomere, telomeric chromatin, trf2, Proteins, Cell Cycle Checkpoints, DNA, Chromatin Assembly and Disassembly, Shelterin, Linker DNA, Molecular biology, biology.protein, lcsh:Q, MESH: Telomere
Abstract: Mammalian telomeres stabilize chromosome ends as a result of their assembly into a peculiar form of chromatin comprising a complex of non-histone proteins named shelterin. TRF2, one of the shelterin components, binds to the duplex part of telomeric DNA and is essential to fold the telomeric chromatin into a protective cap. Although most of the human telomeric DNA is organized into tightly spaced nucleosomes, their role in telomere protection and how they interplay with telomere-specific factors in telomere organization is still unclear. In this study we investigated whether TRF2 can regulate nucleosome assembly at telomeres. By means of chromatin immunoprecipitation (ChIP) and Micrococcal Nuclease (MNase) mapping assay, we found that the density of telomeric nucleosomes in human cells was inversely proportional to the dosage of TRF2 at telomeres. This effect was not observed in the G1 phase of the cell cycle but appeared coincident of late or post-replicative events. Moreover, we showed that TRF2 overexpression altered nucleosome spacing at telomeres increasing internucleosomal distance. By means of an in vitro nucleosome assembly system containing purified histones and remodeling factors, we reproduced the short nucleosome spacing found in telomeric chromatin. Importantly, when in vitro assembly was performed in the presence of purified TRF2, nucleosome spacing on a telomeric DNA template increased, in agreement with in vivo MNase mapping. Our results demonstrate that TRF2 negatively regulates the number of nucleosomes at human telomeres by a cell cycle-dependent mechanism that alters internucleosomal distance. These findings raise the intriguing possibility that telomere protection is mediated, at least in part, by the TRF2-dependent regulation of nucleosome organization.
Published: 2012
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27. CST Meets Shelterin to Keep Telomeres in Check

Author: M. Teresa Teixeira, Vincent Géli, Marie-Josèphe Giraud-Panis, Eric Gilson, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratory of Biology and Pathology of Genomes, Centre National de la Recherche Scientifique (CNRS), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Instabilité du génome et cancérogénèse (IGC), Department of Medical Genetics, Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de biologie et pathologie des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Ganivet, Agnès, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: DNA Replication, Telomerase, [SDV]Life Sciences [q-bio], Telomere-Binding Proteins, CST complex, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cyclin B, Biology, 03 medical and health sciences, DNA, Fungal, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, 0303 health sciences, Telomere biology, 030302 biochemistry & molecular biology, Cell Biology, Telomere, Shelterin, Budding yeast, Cell biology, Shelterin Complex, Multiprotein Complexes, Saccharomycetales, Schizosaccharomyces pombe Proteins, human activities
Abstract: Telomere protection in budding yeast requires the heterotrimer named CST (for Cdc13-Stn1-Ten1). Recent data show that CST components are conserved and required for telomere stability in a wide range of eukaryotes, even those utilizing the shelterin complex to protect their telomeres. A common function of these proteins might be to stimulate priming at the C-strand gap that remains after telomerase elongation, replication termination, and terminal processing. In light of the budding yeast situation, another conserved function of CST might well be the regulation of telomerase. The cohabitation at telomeres of CST and shelterin components highlights the complexity of telomere biology.
Published: 2010
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28. SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair

Author: Sandy Chang, Eric Gilson, Anaïs Poulet, Yung C. Lam, Randy J. Legerski, Peili Gu, Marie Josèphe Giraud-Panis, Shamima Akhter, Susan M. Bailey, Jing Ye, Department of Genetics, The University of Texas Medical Branch (UTMB), Laboratoire de biologie et pathologie des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Environmental and Radiological Health Sciences, Colorado State University [Fort Collins] (CSU), Department of Medical Genetics, Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Hematopathology, Ganivet, Agnès, Laboratory of Biology and Pathology of Genomes, and Centre National de la Recherche Scientifique (CNRS)
Subjects: Exonuclease, chromosomes, DNA Repair, DNA damage, Telomere-Binding Proteins, Cell Cycle Proteins, Ataxia Telangiectasia Mutated Proteins, Protein Serine-Threonine Kinases, Biology, Aminopeptidases, Shelterin Complex, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Molecular Biology, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Nuclease, Tripeptidyl-Peptidase 1, General Immunology and Microbiology, DNA synthesis, Tumor Suppressor Proteins, General Neuroscience, DNA replication, Fibroblasts, Telomere, Embryo, Mammalian, telomeres, Molecular biology, DNA-Binding Proteins, Exodeoxyribonucleases, chemistry, 030220 oncology & carcinogenesis, Knockout mouse, biology.protein, Serine Proteases, DNA
Abstract: Progressive telomere attrition or deficiency of the protective shelterin complex elicits a DNA damage response as a result of a cell's inability to distinguish dysfunctional telomeric ends from DNA double-strand breaks. SNMIB/Apollo is a shelterin-associated protein and a member of the SMN1/PSO2 nuclease family that localizes to telomeres through its interaction with TRF2. Here, we generated SNMIB/Apollo knockout mouse embryo fibroblasts (MEFs) to probe the function of SNMIB/Apollo at mammalian telomeres. SNMIB/Apollo null MEFs exhibit an increased incidence of G2 chromatid-type fusions involving telomeres created by leading-strand DNA synthesis, reflective of a failure to protect these telomeres after DNA replication. Mutations within SNMIB/Apollo's conserved nuclease domain failed to suppress this phenotype, suggesting that its nuclease activity is required to protect leading-strand telomeres. SNMIB/Apollo(-/-)ATM(-/-) MEFs display robust telomere fusions when Trf2 is depleted, indicating that ATM is dispensable for repair of uncapped telomeres in this setting. Our data implicate the 5'-3' exonuclease function of SNM1B/Apollo in the generation of 3' single-stranded overhangs at newly replicated leading-strand telomeres to protect them from engaging the non-homologous end-joining pathway.
Published: 2010

29. Platination of telomeric DNA by cisplatin disrupts recognition by TRF2 and TRF1

Author: Frédérique Magdinier, Simon Amiard, Isabelle Ourliac-Garnier, Eric Gilson, Razan Charif, Sophie Bombard, Marie-Josèphe Giraud-Panis, Keyvan Rezaï, Anaïs Poulet, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Telomeres and Cancer Laboratory, INSTITUT CURIE, Laboratoire Joliot Curie, École normale supérieure - Lyon ( ENS Lyon ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Homéostasie cellulaire et cancer - Reprogrammation des réponses biologiques et thérapies alternatives ( U1007 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Department of Pharmacology Oncology, CRLCC René Huguenin, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Homéostasie cellulaire et cancer - Reprogrammation des réponses biologiques et thérapies alternatives (U1007), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Ganivet, Agnès, Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), and Institut Curie
Subjects: Telomere-Binding Proteins, TRF2, TRF1, Biochemistry, Shelterin Complex, Cell Line, Inorganic Chemistry, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Telomeric Repeat Binding Protein 2, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Antitumour, 030304 developmental biology, Cisplatin, 0303 health sciences, Binding Sites, Chemistry, Chromosome, DNA, Telomere, Molecular biology, In vitro, 3. Good health, Nucleoprotein, Telomeres, Duplex (building), Cell culture, 030220 oncology & carcinogenesis, Telomeric-Repeat Binding Factor, Protein Binding, medicine.drug
Abstract: Telomeres, the nucleoprotein complexes located at the ends of chromosomes, are involved in chromosome protection and genome stability. Telomeric repeat binding factor 1 (TRF1) and telomeric repeat binding factor 2 (TRF2) are the two telomeric proteins that bind to duplex telomeric DNA through interactions between their C-terminal domain and several guanines of the telomeric tract. Since the antitumour drug cisplatin binds preferentially to two adjacent guanines, we have investigated whether cisplatin adducts could affect the binding of TRF1 and TRF2 to telomeric DNA and the property of TRF2 to stimulate telomeric invasion, a process that is thought to participate in the formation of the t-loop. We show that the binding of TRF1 and TRF2 to telomeric sequences selectively modified by one GG chelate of cisplatin is markedly affected by cisplatin but that the effect is more drastic for TRF2 than for TRF1 (3-5-fold more sensitivity for TRF2 than for TRF1). We also report that platinum adducts cause a decrease in TRF2-dependent stimulation of telomeric invasion in vitro. Finally, in accordance with in vitro data, analysis of telomeric composition after cisplatin treatment reveals that 60% of TRF2 dissociate from telomeres.
Published: 2010

30. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends

Author: Oriane Bombarde, Céline BOBY, Dennis Gomez, Philippe Frit, Marie-Josèphe Giraud-Panis, Eric Gilson, Bernard Salles, Patrick Calsou, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratory of Biology and Pathology of Genomes, Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et pathologie des génomes, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: enzymes and coenzymes (carbohydrates), embryonic structures, fungi, DNA repair, telomeres Introduction, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, genome instability, non-homologous end-joining
Abstract: DNA-dependent protein kinase (DNA-PK) is a double-strand breaks repair complex, the subunits of which (KU and DNA-PKcs) are paradoxically present at mammalian telomeres. Telomere fusion has been reported in cells lacking these proteins, raising two questions: how is DNA-PK prevented from initiating classical ligase IV (LIG4)-dependent non-homologous end-joining (C-NHEJ) at telomeres and how is the backup end-joining (EJ) activity (B-NHEJ) that operates at telomeres under conditions of C-NHEJ deficiency controlled? To address these questions, we have investigated EJ using plasmid substrates bearing double-stranded telomeric tracks and human cell extracts with variable C-NHEJ or B-NHEJ activity. We found that (1) TRF2/RAP1 prevents C-NHEJ-mediated end fusion at the initial DNA-PK end binding and activation step and (2) DNA-PK counteracts a potent LIG4-independent EJ mechanism. Thus, telomeres are protected against EJ by a lock with two bolts. These results account for observations with mammalian models and underline the importance of alternative non-classical EJ pathways for telomere fusions in cells.
Published: 2010

31. structural identity of telomeric complexes

Author: Marie-Hélène Le Du, Anaïs Poulet, Marie-Josèphe Giraud-Panis, Eric Gilson, Sabrina Pisano, Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Laboratoire Joliot Curie, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et pathologie des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: DNA Repair, DNA repair, [SDV]Life Sciences [q-bio], Biophysics, Saccharomyces cerevisiae, Computational biology, Cell fate determination, Biology, Biochemistry, Shelterin, 03 medical and health sciences, chemistry.chemical_compound, Structural Biology, Schizosaccharomyces, Genetics, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, DNA binding, Molecular Biology, ComputingMilieux_MISCELLANEOUS, CST, 030304 developmental biology, Mammals, Telomere-binding protein, 0303 health sciences, Oxytricha, 030302 biochemistry & molecular biology, Genetic Variation, Proteins, Robustness (evolution), [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, Cell Biology, Telomere, Nucleoprotein, chemistry, Tandem Repeat Sequences, RNA
Abstract: International audience; A major issue in telomere research is to understand how the integrity of chromosome ends is controlled. Although several nucleoprotein complexes have been described at the telomeres of different organisms, it is still unclear how they confer a structural identity to chromosome ends in order to mask them from DNA repair and to ensure their proper replication. In this review, we describe how telomeric nucleoprotein complexes are structured, comparing different organisms and trying to link these structures to telomere biology. It emerges that telomeres are formed by a complex and specific network of interactions between DNA, RNA and proteins. The fact that these interactions and associated activities are reinforcing each other might help to guaranty the robustness of telomeric functions across the cell cycle and in the event of cellular perturbations. We propose that telomeric nucleoprotein complexes orient cell fate through dynamic transitions in their structures and their organization
Published: 2010
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32. Specific Binding of Cyclic-AMP Receptor Protein to DNA. Effect of the Sequence and of the Introduction of a Nick in the Binding Site

Author: Marie-Josèphe Giraud-Panis, Jean Claude Maurizot, Françoise Culard, and Francine Toulmé
Subjects: Cyclic AMP Receptor Protein, Stereochemistry, Base pair, Molecular Sequence Data, Binding energy, medicine.disease_cause, DNA-binding protein, chemistry.chemical_compound, Structural Biology, medicine, Binding site, Deoxyribonucleases, Type II Site-Specific, Molecular Biology, Escherichia coli, Base Composition, Binding Sites, Base Sequence, Galactose, DNA, General Medicine, Binding constant, chemistry, Biochemistry, Nucleic Acid Conformation, Spectrophotometry, Ultraviolet
Abstract: The binding of Escherichia coli Cyclic AMP Receptor Protein (CRP) to several DNA fragments of about 45 base pairs, bearing the natural lactose or galactose sites, as well as several synthetic related sites, was investigated using fluorescence spectroscopy and gel retardation experiments. The salt dependence of the equilibrium binding constant indicates that CRP makes an identical number of ion pairs with the lac, lacL8 and gal sites although the binding constants are drastically different. However increasing the symmetry of the gal site leads to an increase of the number of ion pairs between the protein and the DNA. A single strand nick was introduced at the centre of a symmetrized gal site and this reduces the binding energy of CRP by about 0.6 Kcal. These results are discussed with respect to the bending constraints imposed on the DNA by the binding of CRP. The results are in agreement with the recently published crystal structure of the CRP complexed with DNA [Schutz, S.C., Shields, G.C. and Steitz, T.A., Science 253, 1001-1007 (1991)] showing that the 90 degrees bending of the DNA in the complex results from two kinks.
Published: 1992
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33. TRF2 promotes, remodels and protects telomeric Holliday junctions

Author: Stephen C. West, Fabien Montel, Rémi Buisson, Stephen C.Y. Ip, Anaïs Poulet, Cendrine Faivre-Moskalenko, Santiago Cuesta-Lopez, Marie-Josèphe Giraud-Panis, Françoise Guerlesquin, Anne-Cécile Déclais, David M.J. Lilley, Julien Moukhtar, Françoise Argoul, Eric Gilson, Melanie Koelblen, Thomas Godet, Olivier Bornet, Simon Amiard, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Interactions et Modulateurs de Réponses (IMR), Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cruciform, MESH: Base Sequence, MESH: Recombinases, MESH: Protein Structure, Tertiary, MESH: Histidine, 0302 clinical medicine, Protein structure, Potassium Permanganate, Holliday junction, Recombinase, Telomeric Repeat Binding Protein 2, Base Pairing, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH: Potassium Permanganate, General Neuroscience, Holliday Junction Resolvases, MESH: Telomeric Repeat Binding Protein 2, Telomere, MESH: Saccharomyces cerevisiae, Branch migration, Cell biology, Biochemistry, Biological Assay, Protein Binding, Protein Structure, Saccharomyces cerevisiae, Molecular Sequence Data, MESH: Base Pairing, Biology, Cleavage (embryo), MESH: Biological Assay, Article, General Biochemistry, Genetics and Molecular Biology, Recombinases, 03 medical and health sciences, Humans, MESH: Protein Binding, Histidine, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Holliday Junction Resolvases, Molecular Biology, 030304 developmental biology, DNA, Cruciform, MESH: Humans, MESH: Molecular Sequence Data, General Immunology and Microbiology, Bacteria, Base Sequence, DNA, biology.organism_classification, Protein Structure, Tertiary, MESH: Bacteria, Homologous recombination, MESH: Telomere, 030217 neurology & neurosurgery, Tertiary, MESH: DNA, Cruciform
Abstract: International audience; The ability of the telomeric DNA-binding protein, TRF2, to stimulate t-loop formation while preventing t-loop deletion is believed to be crucial to maintain telomere integrity in mammals. However, little is known on the molecular mechanisms behind these properties of TRF2. In this report, we show that TRF2 greatly increases the rate of Holliday junction (HJ) formation and blocks the cleavage by various types of HJ resolving activities, including the newly identified human GEN1 protein. By using potassium permanganate probing and differential scanning calorimetry, we reveal that the basic domain of TRF2 induces structural changes to the junction. We propose that TRF2 contributes to t-loop stabilisation by stimulating HJ formation and by preventing resolvase cleavage. These findings provide novel insights into the interplay between telomere protection and homologous recombination and suggest a general model in which TRF2 maintains telomere integrity by controlling the turnover of HJ at t-loops and at regressed replication forks.
Published: 2009
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34. Topoisomerase IIIa is required for normal proliferation and telomere stability in alternative lenghtening of telomeres

Author: Eric Gilson, Emilie Bayart, Lionel Guittat, Arturo Londoño-Vallejo, Marie-Josèphe Giraud-Panis, Thomas Wenner, Jean-François Riou, Mounira Amor-Guéret, Nassima Temime-Smaali, Dennis Gomez, Céline Douarre, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Telomere Recombination, Small interfering RNA, Telomerase, Chromatin Immunoprecipitation, DNA damage, [SDV]Life Sciences [q-bio], Telomere-Binding Proteins, Promyelocytic Leukemia Protein, General Biochemistry, Genetics and Molecular Biology, Shelterin Complex, Article, Cell Line, 03 medical and health sciences, 0302 clinical medicine, Chromosomal Instability, Humans, Telomeric Repeat Binding Protein 2, [INFO]Computer Science [cs], RNA, Small Interfering, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cell Proliferation, Telomere-binding protein, Adenosine Triphosphatases, 0303 health sciences, General Immunology and Microbiology, biology, RecQ Helicases, General Neuroscience, Topoisomerase, Tumor Suppressor Proteins, DNA Helicases, Nuclear Proteins, Telomere, Molecular biology, Neoplasm Proteins, Protein Subunits, DNA Topoisomerases, Type I, 030220 oncology & carcinogenesis, biology.protein, Anaphase, Chromatin immunoprecipitation, Transcription Factors
Abstract: Topoisomerase (Topo) IIIalpha associates with BLM helicase, which is proposed to be important in the alternative lengthening of telomeres (ALT) pathway that allows telomere recombination in the absence of telomerase. Here, we show that human Topo IIIalpha colocalizes with telomeric proteins at ALT-associated promyelocytic bodies from ALT cells. In these cells, Topo IIIalpha immunoprecipitated with telomere binding protein (TRF) 2 and BLM and was shown to be associated with telomeric DNA by chromatin immunoprecipitation, suggesting that these proteins form a complex at telomere sequences. Topo IIIalpha depletion by small interfering RNA reduced ALT cell survival, but did not affect telomerase-positive cell lines. Moreover, repression of Topo IIIalpha expression in ALT cells reduced the levels of TRF2 and BLM proteins, provoked a strong increase in the formation of anaphase bridges, induced the degradation of the G-overhang signal, and resulted in the appearance of DNA damage at telomeres. In contrast, telomere maintenance and TRF2 levels were unaffected in telomerase-positive cells. We conclude that Topo IIIalpha is an important telomere-associated factor, essential for telomere maintenance and chromosome stability in ALT cells, and speculate on its potential mechanistic function.
Published: 2008
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35. NMR studies of telomeric nucleoprotein complexes involving the Myb-like domain of the human telomeric protein TRF2

Author: Françoise Paquet, Marie-Josèphe Giraud-Panis, Hervé Meudal, Gérard Lancelot, Yann Bilbille, Centre de biophysique moléculaire (CBM), and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: animal structures, General Chemical Engineering, NMR spectrometry, Protooncogene, 010402 general chemistry, 01 natural sciences, DNA-binding protein, 03 medical and health sciences, chemistry.chemical_compound, MYB, Transcription factor, 030304 developmental biology, Nucleoprotein, 0303 health sciences, fungi, Molecular interaction, General Chemistry, DNA, Telomere, Random coil, 0104 chemical sciences, chemistry, Biochemistry, Duplex (building), Biophysics, Molecular complex, Human
Abstract: In order to study the binding of the Myb-like domain of the human telomeric protein TRF2 (Myb-TRF2) with different structural components of the t-loop model, we report NMR studies of the binding of Myb-TRF2 protein with two repeats human telomeric DNA under three conformations. Our results showed that Myb-TRF2 binds to the duplex and even to the quadruplex and the random coil G-rich strand. The solution structure of Myb-TRF2 reported here looks like Myb-TRF1 suggesting similar DNA binding mode. As a matter of fact, we have shown that its binding to the human telomeric duplex presents great similarities with this of Myb-TRF1.
Published: 2006
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36. The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair

Author: Michele Brunori, Simon Amiard, Serge Bauwens, Christelle Lenain, Eric Gilson, Marie-Josèphe Giraud-Panis, ProdInra, Migration, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Unité mixte de recherche biologie moléculaire de la cellule, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), École normale supérieure - Cachan (ENS Cachan), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Exonuclease, DNA repair, DNA damage, Recombinant Fusion Proteins, Apollo, TELOMERE, DNA Exonuclease, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, TRF2, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chlorocebus aethiops, Animals, Humans, Telomeric Repeat Binding Protein 2, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Glutathione Transferase, Genetics, 0303 health sciences, biology, Agricultural and Biological Sciences(all), Biochemistry, Genetics and Molecular Biology(all), Chromosome, Nuclear Proteins, biology.organism_classification, GENOMIQUE, 3. Good health, Telomere, DNA Repair Enzymes, Exodeoxyribonucleases, chemistry, 030220 oncology & carcinogenesis, DNA REPAIR, COS Cells, biology.protein, General Agricultural and Biological Sciences, DNA
Abstract: SummaryA major issue in telomere research is to understand how the integrity of chromosome ends is preserved [1, 2]. The human telomeric protein TRF2 coordinates several pathways that prevent checkpoint activation and chromosome fusions [3–9]. In this work, we identified hSNM1B [10], here named Apollo, as a novel TRF2-interacting factor. Interestingly, the N-terminal domain of Apollo is closely related to that of Artemis, a factor involved in V(D)J recombination and DNA repair [11]. Both proteins belong to the β-CASP metallo-β-lactamase family of DNA caretaker proteins [12, 13]. Apollo appears preferentially localized at telomeres in a TRF2-dependent manner. Reduced levels of Apollo exacerbate the sensitivity of cells to TRF2 inhibition, resulting in severe growth defects and an increased number of telomere-induced DNA-damage foci and telomere fusions. Purified Apollo protein exhibits a 5′-to-3′ DNA exonuclease activity. We conclude that Apollo is a novel component of the human telomeric complex and works together with TRF2 to protect chromosome termini from being recognized and processed as DNA damage. These findings unveil a previously undescribed telomere-protection mechanism involving a DNA 5′-to-3′ exonuclease.
Published: 2006
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37. The G-quadruplex ligand telomestatin inhibits POT1 binding to telomeric sequences in vitro and induces GFP-POT1 dissociation from telomeres in human cells

Author: Jean-François Riou, Marie-Françoise O'Donohue, Jérome Macadré, Céline Douarre, Alain Kolkes, Hervé Kaplan, Kazuo Shin-ya, Pascale Koebel, Marie-Josèphe Giraud-Panis, Thomas Wenner, Dennis Gomez, Laboratoire d'Onco-Pharmacologie (LOP), Centre National de la Recherche Scientifique (CNRS), Médicaments : Dynamique Intracellulaire et Architecture Nucléaire (MéDIAN), Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Joliot Curie, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), Biomolécules : interactions moléculaires, cellulaires et cellules-matrice extracellulaire (BIMCCME), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie moléculaire eucaryote (LBME), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-JE2428, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie et pathologie des génomes, Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine de Reims, Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Laboratory of Biology and Pathology of Genomes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, Telomere localization, Telomere Capping, Recombinant Fusion Proteins, [SDV]Life Sciences [q-bio], Green Fluorescent Proteins, Telomere-Binding Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 010402 general chemistry, G-quadruplex, Kidney, Transfection, 01 natural sciences, Telomestatin, Shelterin Complex, Green fluorescent protein, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Humans, Telomeric Repeat Binding Protein 2, Oxazoles, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Telomere-binding protein, 0303 health sciences, Nuclear Proteins, DNA, Telomere, Molecular biology, 0104 chemical sciences, G-Quadruplexes, Oncology, chemistry, Cancer cell, TATA Box Binding Protein-Like Proteins, Protein Binding
Abstract: Telomestatin is a potent G-quadruplex ligand that specifically interacts with the 3′ telomeric overhang, leading to its degradation and that induces a delayed senescence and apoptosis of cancer cells. Protection of Telomere 1 (POT1) was recently identified as a specific single-stranded telomere-binding protein involved in telomere capping and T-loop maintenance. We showed here that a telomestatin treatment inhibits POT1 binding to the telomeric overhang in vitro. The treatment of human EcR293 cells by telomestatin induces a dramatic and rapid delocalization of POT1 from its normal telomere sites but does not affect the telomere localization of the double-stranded telomere-binding protein TRF2. Thus, we propose that G-quadruplex stabilization at telomeric G-overhang inactivates POT1 telomeric function, generating a telomere dysfunction in which chromosome ends are no longer properly protected. (Cancer Res 2006; 66(14): 6908-12)
Published: 2006
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38. Drosophila DSP1 and rat HMGB1 have equivalent DNA binding properties and share a similar secondary fold

Author: Daniel Locker, Marie-Josèphe Giraud-Panis, Martine Decoville, Carsten Janke, Davy Martin, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and LEGOUPIL, Laëtitia
Subjects: DNA Ligases, Transcription, Genetic, [SDV]Life Sciences [q-bio], Glutamine, Sequence alignment, Biology, HMGB1, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, medicine, Animals, Drosophila Proteins, HMGB2 Protein, HMGB1 Protein, Molecular Biology, 030304 developmental biology, Cisplatin, chemistry.chemical_classification, Genetics, 0303 health sciences, Circular Dichroism, 030302 biochemistry & molecular biology, High Mobility Group Proteins, General Medicine, DNA, biology.organism_classification, Chromatin, Recombinant Proteins, Amino acid, Cell biology, Rats, [SDV] Life Sciences [q-bio], Drosophila melanogaster, chemistry, biology.protein, Linker, medicine.drug, Plasmids
Abstract: International audience; The protein DSP1 belongs to the group of HMG-box proteins, which share the common structural feature of the HMG-box. This approximately 80 amino acid long motif binds DNA via the minor groove. DSP1 was discovered as a transcriptional co-repressor of Dorsal in Drosophila melanogaster and then was shown to participate to the remodeling of chromatin. By means of sequence alignment and gene organization, DSP1 was classified as the fly homologue of the vertebrate proteins HMGB1/2. DSP1 contains two HMG boxes flanked by two glutamine-rich domains at the N-terminus. In addition, the HMG domain of DSP1 displays two differences in its primary sequence as compared to the vertebrate HMGB1: a shorter acidic tail and a linker between the two boxes longer by 6 amino acids. By comparing several functional parameters of DSP1 with those of HMGB1, the present study establishes the functional equivalence of both proteins in terms of DNA recognition. The major structural difference between the two proteins, the glutamine-rich N-terminal tail of DSP1, which does not exist in HMGB1, did not interfere with any of the studied DNA-binding properties of the proteins.
Published: 2003

39. Erratum to: 'Interstrand cross-links of cisplatin induce striking distortions in DNA'

Author: Marie-Josèphe Giraud-Panis, Jean-Marc Malinge, M. Leng, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), LEGOUPIL, Laëtitia, and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: Cisplatin, Stereochemistry, [SDV]Life Sciences [q-bio], education, food and beverages, Biochemistry, carbohydrates (lipids), Inorganic Chemistry, [SDV] Life Sciences [q-bio], chemistry.chemical_compound, chemistry, hemic and lymphatic diseases, parasitic diseases, medicine, DNA, medicine.drug
Abstract: International audience; Erratum to: ‘‘Interstrand cross-links of cisplatin induce striking distortions in DNA’’ [J. Inorg. Biochem. 77 (1999) 23–29]
Published: 2000
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40. Transplatin-modified oligonucleotides as modulators of gene expression

Author: Marie-Josèphe Giraud-Panis and Marc Leng
Subjects: inorganic chemicals, Stereochemistry, Oligonucleotides, Adduct, chemistry.chemical_compound, DNA Adducts, medicine, Humans, Pharmacology (medical), Nucleotide, Bifunctional, Pharmacology, Cisplatin, chemistry.chemical_classification, Binding Sites, Oligonucleotide, DNA, Gene Expression Regulation, Neoplastic, Cross-Linking Reagents, chemistry, Biochemistry, Helix, Isomerization, medicine.drug
Abstract: Transplatin [trans-diamminedichloroplatinum(II)], contrary to its stereoisomer cisplatin, is clinically inactive. However, like cisplatin, it binds to DNA. In the first part of this review, some results on the interactions between transplatin and double-stranded DNA are presented. The major bifunctional adducts are interstrand cross-links. Intrastrand cross-links are not formed. On the other hand, intrastrand cross-links are formed in the reaction between single-stranded DNA and transplatin. Some properties of the intrastrand cross-links at GNG sites (N is a nucleotide) are described. The (G1,G3)-intrastrand cross-links rearrange into interstrand cross-links as soon as the platinated oligonucleotides are paired with their complementary strands. The linkage isomerization reaction is exclusively triggered by the formation of a double helix. The potential use of these platinated oligonucleotides to block the cellular machinery specifically and irreversibly is discussed.
Published: 2000

41. Interstrand cross-links of cisplatin induce striking distortions in DNA

Author: M. Leng, Marie-Josèphe Giraud-Panis, Jean-Marc Malinge, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), LEGOUPIL, Laëtitia, and Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Stereochemistry, [SDV]Life Sciences [q-bio], Crystal structure, Biochemistry, Adduct, Inorganic Chemistry, DNA Adducts, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, medicine, Humans, Molecule, Bifunctional, 030304 developmental biology, Cisplatin, 0303 health sciences, Oligonucleotide, DNA, [SDV] Life Sciences [q-bio], Cross-Linking Reagents, chemistry, 030220 oncology & carcinogenesis, Helix, Nucleic Acid Conformation, Female, medicine.drug
Abstract: International audience; In the reaction between cellular DNA and cisplatin, different bifunctional adducts are formed including intrastrand and interstrand cross-links. The respective role of these lesions in the cytotoxicity of the drug is not yet elucidated. This paper deals with the current knowledge on cisplatin interstrand cross-links and presents results on the formation, stability and structure of these adducts. A key step in the studies of these lesions is the recent determination of solution and crystallographic structures of double-stranded oligonucleotides containing a unique interstrand cross-link. The DNA distortions induced by this adduct exhibit unprecedented features such as the location of the platinum residue in the minor groove, the extrusion of the cytosines of the cross-linked d(GpC).d(GpC) site, the bending of the helix axis towards the minor groove and a large DNA unwinding. In addition to a detailed determination of the distortions, the high resolution of the crystal structure allowed us to locate the water molecules surrounding the adduct. The possible implications of this structure for the chemical properties and the cellular processing of cisplatin interstrand cross-links are discussed.
Published: 1999
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42. Structure of the four-way DNA junction and its interaction with proteins

Author: Alastair I.H. Murchie, Marie-Josèphe Giraud-Panis, Derek R. Duckett, David Malcolm James Lilley, and J. Richard G. Pöhler
Subjects: Recombination, Genetic, Chemistry, Stacking, DNA, Antiparallel (biochemistry), General Biochemistry, Genetics and Molecular Biology, Metal, DNA-Binding Proteins, Crystallography, chemistry.chemical_compound, Biochemistry, visual_art, Phosphodiester bond, visual_art.visual_art_medium, Nucleic Acid Conformation, General Agricultural and Biological Sciences, Recombination, Minor groove
Abstract: The four-way DNA junction is an important intermediate in recombination processes; it is, the substrate for different enzyme activities. In solution, the junction adopts a right-handed, antiparallel-stacked X -structure formed by the pairwise coaxial-stacking of helical arms. The stereochemistry is determined by the juxtaposition of grooves and backbones, which is optimal when the smaller included angle is 60°. The antiparallel structure has two distinct sides with major and minor groove-characteristics, respectively. The folding process requires the binding of metal cations, in the absence of which, the junction remains extended without helix-helix stacking. The geometry of the junction can be perturbed by the presence of certain base-base mispairs or phosphodiester discontinuities located at the point of strand exchange. The four-way DNA junction is selectively cleaved by a number of resolving enzymes. In a number of cases, these appear to recognize the minor groove face of the junction and are functionally divisible into activities that recognize and bind the junction, and a catalytic activity. Some possible mechanisms for the recognition of branched DNA structure are discussed.
Published: 1995

43. 110 T4 Endonuclease VII — a zinc containing four-way DNA junction resolving enzyme

Author: J. Richard G. Pöhler, Marie-Josèphe Giraud-Panis, and David M.J. Lilley
Subjects: chemistry.chemical_classification, chemistry.chemical_compound, Enzyme, chemistry, chemistry.chemical_element, Zinc, T4 endonuclease VII, Biochemistry, Zinc finger nuclease, Molecular biology, DNA
Published: 1997
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44. The N-terminal domains of TRF1 and TRF2 regulate their ability to condense telomeric DNA

Author: Eric Gilson, Anaïs Poulet, Françoise Argoul, Frédéric Brunet, Nicolas Hugo, Bei Pei, Yann-Vaï Le Bihan, Marie-Josèphe Giraud-Panis, Simon Amiard, Fabien Montel, Annie Chaboud, Marie-Hélène Ledu, Sabrina Pisano, Cendrine Faivre-Moskalenko, Zofia Haftek-Terreau, Yannick Tauran, Institut de Physique Nucléaire d'Orsay (IPNO), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre scientifique et Technique Jean Feger (CSTJF), TOTAL FINA ELF, Laboratoire de Physique de l'ENS Lyon (Phys-ENS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), BioSciences Lyon-Gerland (BLG), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
Subjects: HMG-box, [SDV]Life Sciences [q-bio], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Molecular Sequence Data, Biology, Evolution, Molecular, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Protein structure, Genetics, Humans, Telomeric Repeat Binding Protein 2, Amino Acid Sequence, Telomeric Repeat Binding Protein 1, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Sequence Homology, Amino Acid, RNA, DNA, Telomere, Protein Structure, Tertiary, DNA binding site, chemistry, 030217 neurology & neurosurgery, Binding domain
Abstract: TRF1 and TRF2 are key proteins in human telomeres, which, despite their similarities, have different behaviors upon DNA binding. Previous work has shown that unlike TRF1, TRF2 condenses telomeric, thus creating consequential negative torsion on the adjacent DNA, a property that is thought to lead to the stimulation of single-strand invasion and was proposed to favor telomeric DNA looping. In this report, we show that these activities, originating from the central TRFH domain of TRF2, are also displayed by the TRFH domain of TRF1 but are repressed in the full-length protein by the presence of an acidic domain at the N-terminus. Strikingly, a similar repression is observed on TRF2 through the binding of a TERRA-like RNA molecule to the N-terminus of TRF2. Phylogenetic and biochemical studies suggest that the N-terminal domains of TRF proteins originate from a gradual extension of the coding sequences of a duplicated ancestral gene with a consequential progressive alteration of the biochemical properties of these proteins. Overall, these data suggest that the N-termini of TRF1 and TRF2 have evolved to finely regulate their ability to condense DNA.
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45. T4 endonuclease VII--a zinc containing four-way DNA junction resolving enzyme

Author: Marie-Josèphe Giraud-Panis, Jr, Pöhler, and Dm, Lilley
Subjects: Models, Molecular, Zinc, Binding Sites, Endodeoxyribonucleases, Sequence Homology, Amino Acid, Protein Conformation, DNA, Viral, Molecular Sequence Data, Bacteriophage T4, Nucleic Acid Conformation, Amino Acid Sequence, Sequence Alignment

46. Recognition and manipulation of branched DNA structure by junction-resolving enzymes

Author: Mf, White, Marie-Josèphe Giraud-Panis, Jr, Pöhler, and Dm, Lilley
Subjects: Recombination, Genetic, Endodeoxyribonucleases, DNA Repair, Models, Genetic, Sequence Homology, Amino Acid, Protein Conformation, Molecular Sequence Data, CHO Cells, Saccharomyces cerevisiae, DNA-Binding Proteins, Cricetinae, Viruses, Animals, Nucleic Acid Conformation, Amino Acid Sequence
Abstract: The junction-resolving enzymes are a class of nucleases that introduce paired cleavages into four-way DNA junctions. They are important in DNA recombination and repair, and are found throughout nature, from eubacteria and their bacteriophages through to higher eukaryotes and their viruses. These enzymes exhibit structure-selective binding to DNA junctions; although cleavage may be more or less sequence-dependent, binding affinity is purely related to the branched structure of the DNA. Binding and cleavage events can be separated for a number of the enzymes by mutagenesis, and mutant proteins that are defective in cleavage while retaining normal junction-selective binding have been isolated. Critical acidic residues have been identified in several resolving enzymes, suggesting a role in the coordination of metal ions that probably deliver the hydrolytic water molecule. The resolving enzymes all bind to junctions in dimeric form, and the subunits introduce independent cleavages within the lifetime of the enzyme-junction complex to ensure resolution of the four-way junction. In addition to recognising the structure of the junction, recent data from four different junction-resolving enzymes indicate that they also manipulate the global structure. In some cases this results in severe distortion of the folded structure of the junction. Understanding the recognition and manipulation of DNA structure by these enzymes is a fascinating challenge in molecular recognition.

47. A topological mechanism for TRF2-enhanced strand invasion

Author: Marie-Josèphe Giraud-Panis, Philippe Bouvet, Simon Amiard, Michel Doudeau, Alessandro Vindigni, Sébastien Pinte, Cendrine Faivre-Moskalenko, Dimitar Angelov, Anaïs Poulet, Jacques Paoletti, Christelle Lenain, Nele Hug, Eric Gilson, Unité mixte de recherche biologie moléculaire de la cellule, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'histoire du temps présent (IHTP), Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Cachan (ENS Cachan), Swiss Institute for Experimental Cancer Research, International Centre for Genetic Engineering and Biotechnology (ICGEB), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Joliot Curie, École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique de l'ENS Lyon (Phys-ENS), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Swiss Institute for Experimental Cancer Research - Lausanne (ISREC), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: HMG-box, [SDV]Life Sciences [q-bio], Mutant, TELOMERE, TRF2, Biology, Microscopy, Atomic Force, Topology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Telomere Homeostasis, D-loop, Structural Biology, Humans, Telomeric Repeat Binding Protein 2, [INFO]Computer Science [cs], Telomeric Repeat Binding Protein 1, Strand invasion, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, DNA, Superhelical, DNA, GENOMIQUE, 3. Good health, Telomere, chemistry, 030220 oncology & carcinogenesis, Nucleic Acid Conformation, DNA supercoil
Abstract: Telomeres can fold into t-loops that may result from the invasion of the 3' overhang into duplex DNA. Their formation is facilitated in vitro by the telomeric protein TRF2, but very little is known regarding the mechanisms involved. Here we reveal that TRF2 generates positive supercoiling and condenses DNA. Using a variety of TRF2 mutants, we demonstrate a strong correlation between this topological activity and the ability to stimulate strand invasion. We also report that these properties require the combination of the TRF-homology (TRFH) domain of TRF2 with either its N- or C-terminal DNA-binding domains. We propose that TRF2 complexes, by constraining DNA around themselves in a right-handed conformation, can induce untwisting of the neighboring DNA, thereby favoring strand invasion. Implications of this topological model in t-loop formation and telomere homeostasis are discussed.
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48. Functional interaction between poly(ADP-Ribose) polymerase 2 (PARP-2) and TRF2: PARP activity negatively regulates TRF2

Author: Inès Schultz, Isabel Jaco, Jean-Christophe Amé, Marie-Josèphe Giraud-Panis, Gilbert de Murcia, Valérie Schreiber, Catherine-Elaine Koering, Josiane Ménissier-de Murcia, Eric Gilson, Maria A. Blasco, Françoise Dantzer, Cancérogenèse et mutagenèse moléculaire et structurale (CMMS), Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Department of Immunology and Oncology (CSIC), Universidad Autonoma de Madrid (UAM), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité mixte de recherche biologie moléculaire de la cellule, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon), ProdInra, Migration, Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universidad Autónoma de Madrid (UAM), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: Telomerase, DNA damage, Poly ADP ribose polymerase, [SDV]Life Sciences [q-bio], Biology, [INFO] Computer Science [cs], Chromatids, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Mice, Animals, Humans, MYB, Telomeric Repeat Binding Protein 2, [INFO]Computer Science [cs], Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Telomere-binding protein, 0303 health sciences, Binding Sites, 030302 biochemistry & molecular biology, Cell Biology, Base excision repair, DNA, Fibroblasts, Telomere, GENETIQUE, Molecular biology, Chromosomes, Mammalian, DNA Dynamics and Chromosome Structure, Protein Structure, Tertiary, [SDV] Life Sciences [q-bio], Protein Transport, chemistry, Poly(ADP-ribose) Polymerases, Gene Deletion, DNA Damage, Protein Binding
Abstract: The DNA damage-dependent poly(ADP-ribose) polymerase-2 (PARP-2) is, together with PARP-1, an active player of the base excision repair process, thus defining its key role in genome surveillance and protection. Telomeres are specialized DNA-protein structures that protect chromosome ends from being recognized and processed as DNA strand breaks. In mammals, telomere protection depends on the T(2)AG(3) repeat binding protein TRF2, which has been shown to remodel telomeres into large duplex loops (t-loops). In this work we show that PARP-2 physically binds to TRF2 with high affinity. The association of both proteins requires the N-terminal domain of PARP-2 and the myb domain of TRF2. Both partners colocalize at promyelocytic leukemia bodies in immortalized telomerase-negative cells. In addition, our data show that PARP activity regulates the DNA binding activity of TRF2 via both a covalent heteromodification of the dimerization domain of TRF2 and a noncovalent binding of poly(ADP-ribose) to the myb domain of TRF2. PARP-2(-/-) primary cells show normal telomere length as well as normal telomerase activity compared to wild-type cells but display a spontaneously increased frequency of chromosome and chromatid breaks and of ends lacking detectable T(2)AG(3) repeats. Altogether, these results suggest a functional role of PARP-2 activity in the maintenance of telomere integrity.
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49. Dynamique et régulation des assemblages nucléoprotéiques des télomères humains : Fonctions de la protéine TRF2

Author: simon amiard, Frapart, Isabelle, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Université d'Orléans, and Marie-Josèphe Giraud-Panis
Subjects: topology, Apollon, [SDV]Life Sciences [q-bio], jonction de Holliday, Holliday junction, TRF2, Telomere, Télomères, t-loop, [SDV] Life Sciences [q-bio], boucle T, invasion télomérique, telomeric invasion, Apollo, topologie
Abstract: TRF2 is a key protein in the dynamic of telomere, these regions at the end of linear chromosomes that protect and stabilize chromosome ends. Telomeres can fold into t-loops that were proposed to result from the invasion of the 3' overhang of telomeres into duplex DNA. Their formation is facilitated in vitro by the telomeric protein TRF2, but very little is known regarding the mechanisms involved. We reveal that TRF2 generates positive supercoiling and condenses DNA. Using a variety of TRF2 mutants, we demonstrated a strong correlation between this topological activity and the ability to stimulate strand invasion. We propose that TRF2 complexes, by wrapping DNA around themselves in a right-handed manner induce untwisting of the neighboring DNA, thereby favoring strand invasion. In addition, we demonstrate that the N-terminal domain of TRF2 is a second DNA binding domain which posesses a strong affinity a the Holliday Junction structure. The last part of this thesis reports the identification of the 5' exonuclease activity of Apollo, a new telomeric protein involved in telomeric protection. The results presented give fresh insight in new TRF2 functions that have many implications in telomere biology and in particular the role of TRF2 in t-loop formation., La protéine TRF2 est une protéine clé dans la dynamique des télomères, ces structures nucléoprotéiques présentes à l'extrémité des chromosomes linéaires et responsables de leur protection. Bien que la manière dont les télomères s'organisent pour protéger l'ADN soit encore méconnue, il a été montré récemment que TRF2 est à l'origine de la formation d'une structure en boucle, ou boucle télomérique qui empêcherait les extrémités télomériques d'être reconnus comme des coupures double brin. Un modèle propose que TRF2 permette la formation de cette boucle en induisant l'invasion du simple brin télomérique terminal à l'intérieur de la séquence double brin après repliement du télomère sur lui même. Les études réalisées lors de cette thèse montrent que TRF2 est en mesure de stimuler l'invasion télomérique de manière indirecte facilitant l'ouverture de la double hélice grâce à des modifications d'ordre topologique de l'ADN cible. Par ailleurs, les travaux réalisés mettent également en évidence un second mode de fixation à l'ADN de TRF2, par l'intermédiaire de son domaine N-terminal qui possède une affinité remarquable pour la structure des jonctions de Holliday. La dernière partie de cette thèse met en évidence l'activité 5' exonucléase d'une nouvelle protéine télomérique, la protéine Apollon, qui serait impliquée dans la protection des télomères. Tous ces résultats participent à une meilleure compréhension du fonctionnement de TRF2 sur les télomères et en particulier de son rôle dans la formation de la boucle télomérique.
Published: 2007

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