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Your search keyword '"Viola Nähse"' showing total 5 results
Start Over Author "Viola Nähse" Topic 0302 clinical medicine
5 results on '"Viola Nähse"'

1. FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability

Author

Claude Saint-Ruf, Viviana Barra, Silvia Ravera, Philippe Fernandes, Viola Nähse, Enrico Cappelli, Valeria Naim, Benoit Miotto, Maha Said, Intégrité du génome et cancers (IGC), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Università degli studi di Palermo - University of Palermo, The Norwegian Radium Hospital [Oslo, Norway] (TNRH), University of Genoa (UNIGE), Istituto Giannina Gaslini, Genova, Immunologia Clinica e Sperimentale, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-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)-Université Paris Cité (UPCité), Università degli studi di Genova = University of Genoa (UniGe), Miotto, Benoit, Fernandes P., Miotto B., Saint-Ruf C., Said M., Barra V., Nahse V., Ravera S., Cappelli E., and Naim V.

Subjects
0301 basic medicine, Genome instability, musculoskeletal diseases, Transcription, Genetic, QH301-705.5, Regulator, Medicine (miscellaneous), Mitochondrion, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Biochemistry, Genetics and Molecular Biology, Oxidative Phosphorylation, Article, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Stress, Physiological, hemic and lymphatic diseases, Gene expression, FANCD2, Humans, Biology (General), Gene, Ubiquitins, Chromosomal fragile site, Chromosome Fragile Sites, Chromosome Fragility, Fanconi Anemia Complementation Group D2 Protein, DNA damage and repair, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, HCT116 Cells, Cell biology, Mitochondria, Settore BIO/18 - Genetica, 030104 developmental biology, Gene Expression Regulation, 030220 oncology & carcinogenesis, Unfolded Protein Response, General Agricultural and Biological Sciences, DNA Damage
Abstract

Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability involves transcription- and replication-dependent mechanisms. Here, we uncover a role for the mitochondrial stress response pathway in the regulation of CFS stability in human cells. We show that FANCD2, a master regulator of CFS stability, dampens the activation of the mitochondrial stress response and prevents mitochondrial dysfunction. Genetic or pharmacological activation of mitochondrial stress signaling induces CFS gene expression and concomitant relocalization to CFSs of FANCD2. FANCD2 attenuates CFS gene transcription and promotes CFS gene stability. Mechanistically, we demonstrate that the mitochondrial stress-dependent induction of CFS genes is mediated by ubiquitin-like protein 5 (UBL5), and that a UBL5-FANCD2 dependent axis regulates the mitochondrial UPR in human cells. We propose that FANCD2 coordinates nuclear and mitochondrial activities to prevent genome instability., Fernandes et al. discover a connection between the mitochondrial stress response and genomic stability. They find that transcription of common fragile site (CFS) genes is induced by mitochondrial stress, whereas a regulator of CFS stability, FANCD2, acts to dampen the mitochondrial stress response and transcription-associated replication stress. These findings suggest a FANCD2-mediated coordination of nuclear and mitochondrial responses to stress.

Published
2021
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2. JIP4 is recruited by the phosphoinositide-binding protein Phafin2 to promote recycling tubules on macropinosomes

Author

Harald Stenmark, Coen Campsteijn, Andreas Brech, Kay Oliver Schink, Viola Nähse, and Kia Wee Tan

Subjects
Gene isoform, Retromer, Endosome, ESCRT machinery, media_common.quotation_subject, Vesicular Transport Proteins, Endosomes, Mitochondrion, Biology, Phosphatidylinositols, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Microtubule, Humans, Phosphatidylinositol, Internalization, 030304 developmental biology, media_common, Adaptor Proteins, Signal Transducing, VAMP3, Macropinocytosis, 0303 health sciences, Trafficking, Pinocytosis, Cell Biology, Transmembrane protein, Cell biology, Pleckstrin homology domain, Protein Transport, chemistry, Membrane recycling, Carrier Proteins, 030217 neurology & neurosurgery, Protein Binding, Research Article
Abstract

Macropinocytosis allows cells to take up extracellular material in a non-selective manner into large vesicles called macropinosomes. After internalization, macropinosomes acquire phosphatidylinositol 3-phosphate (PtdIns3P) on their limiting membrane as they mature into endosomal-like vesicles. The molecular mechanisms that underlie recycling of membranes and transmembrane proteins from these macropinosomes still need to be defined. Here, we report that JIP4 (officially known as SPAG9), a protein previously described to bind to microtubule motors, is recruited to tubulating subdomains on macropinosomes by the PtdIns3P-binding protein Phafin2 (officially known as PLEKHF2). These JIP4-positive tubulating subdomains on macropinosomes contain F-actin, the retromer recycling complex and the retromer cargo VAMP3. Disruption of the JIP4–Phafin2 interaction, deletion of Phafin2 or inhibition of PtdIns3P production by VPS34 impairs JIP4 recruitment to macropinosomes. Whereas knockout of JIP4 suppresses tubulation, its overexpression enhances tubulation from macropinosomes. JIP4-knockout cells display increased retention of macropinocytic cargo in both early and late macropinosomes. Collectively, these data identify JIP4 and Phafin2 as components of a tubular recycling pathway that operates from macropinosomes. This article has an associated First Person interview with the first author of the paper., Summary: The motor adaptor JIP4 is recruited to macropinosomes by the PtdIns3P-binding protein Phafin2 to promote recycling to the plasma membrane via tubular extensions of macropinosomes.

Published
2021

3. Transcription-dependent regulation of replication dynamics modulates genome stability

Author

Marion Blin, Caroline Brossas, Gaël A. Millot, Mélanie Schmidt, Viola Nähse, Marie-Noëlle Prioleau, Michelle Debatisse, Benoît Le Tallec, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institute for Cancer Research [Oslo], Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), The M.D. team is supported by the Agence Nationale de la Recherche (grant ANR-13-BSV6-0008-01/FRA-Dom), the Association pour la Recherche sur le Cancer (grant Subvention Libre Sl220130607073), and the Institut National du Cancer (grants INCa subventions 2013-103 and PLBIO17-194). The M.N.P. team is supported by the Association pour la Recherche sur le Cancer (grant Labellisation PGA120150202272) and the Agence Nationale de la Recherche (grant ANR-15-CE12-0004-01). M.B. was supported by fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche and the Ligue contre le cancer., We thank S. Lambert and O. Hyrien for critical reading of the manuscript. The authors would like to acknowledge the Cell and Tissue Imaging Platform – PICT-IBiSA (member of France-Bioimaging) of the Genetics and Developmental Biology Department (UMR3215/U934) of Institut Curie for help with light microscopy, the Flow Cytometry Platform Imagoseine of Institut Jacques Monod, Université Paris Diderot, and the Imaging and Cytometry Platform (PFIC) of Institut Gustave Roussy for assistance with cell sorting., ANR-13-BSV6-0008,FRA-Dom,Chorégraphie des domaines de la chromatine au cours de la différenciation: réorganisation des profils de réplication et des sites fragiles communs(2013), Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Faculté de Chirurgie Dentaire (UPD5 Odontologie), Université Paris Descartes - Paris 5 (UPD5), and Institut Curie

Subjects
DNA Replication, MESH: Genomic Instability / physiology, Transcription, Genetic, [SDV]Life Sciences [q-bio], Mitosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endogeny, Biology, Genomic Instability, 03 medical and health sciences, 0302 clinical medicine, Structural Biology, Transcription (biology), MESH: Transcription, Genetic / genetics, MESH: DNA Replication / genetics, Animals, Humans, MESH: Animals, MESH: Chromosome Fragile Sites / genetics, MESH: Genomic Instability / genetics, Molecular Biology, Gene, 030304 developmental biology, Genome stability, 0303 health sciences, Replication timing, MESH: Humans, MESH: Mitosis / physiology, Chromosome Fragile Sites, Chromosomal fragile site, Promoter, Cell biology, MESH: Mitosis / genetics, MESH: Chromosome Fragile Sites / physiology, Fragile sites, MESH: DNA Replication / physiology, Transcription, Origin selection, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

International audience; Common fragile sites (CFSs) are loci that are hypersensitive to replication stress and hotspots for chromosomal rearrangements in cancers. CFSs replicate late in S phase, are cell-type specific and nest in large genes. The relative impact of transcription-replication conflicts versus a low density in initiation events on fragility is currently debated. Here we addressed the relationships between transcription, replication, and instability by manipulating the transcription of endogenous large genes in chicken and human cells. We found that inducing low transcription with a weak promoter destabilized large genes, whereas stimulating their transcription with strong promoters alleviated instability. Notably, strong promoters triggered a switch to an earlier replication timing, supporting a model in which high transcription levels give cells more time to complete replication before mitosis. Transcription could therefore contribute to maintaining genome integrity, challenging the dominant view that it is exclusively a threat.

Published
2018
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4. Transcription-mediated organization of the replication initiation program across large genes sets common fragile sites genome-wide

Author

Anne-Marie Lachages, St eacutephane Koundrioukoff, Bernard Dutrillaux, Yan Jaszczyszyn, Michelle Debatisse, Chun-Long Chen, Viola Nähse, Sami El-Hilali, Olivier Brison, Claude Thermes, Mélanie Schmidt, Dana Azar, Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Institut Curie [Paris]-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), Université Saint-Joseph de Beyrouth (USJ), Oslo University Hospital [Oslo], Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-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 Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Institut Curie-Sorbonne Université (SU)-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), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), and Université des Antilles (UA)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Sorbonne Université (SU)-Muséum national d'Histoire naturelle (MNHN)

Subjects
0301 basic medicine, Genome instability, Transcription, Genetic, DNA Replication Timing, Science, General Physics and Astronomy, Replication Origin, Biology, Genome, Genomic Instability, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, S Phase, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Directionality, lcsh:Science, Gene, Communication and replication, Genetics, Replication timing, Multidisciplinary, Chromosome Fragile Sites, Chromosomal fragile site, General Chemistry, 030104 developmental biology, Replication Initiation, Transcription Termination, Genetic, 030220 oncology & carcinogenesis, lcsh:Q, Fragile sites
Abstract

Common fragile sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Most CFSs nest in large expressed genes, suggesting that transcription could elicit their instability; however, the underlying mechanisms remain elusive. Genome-wide replication timing analyses here show that stress-induced delayed/under-replication is the hallmark of CFSs. Extensive genome-wide analyses of nascent transcripts, replication origin positioning and fork directionality reveal that 80% of CFSs nest in large transcribed domains poor in initiation events, replicated by long-travelling forks. Forks that travel long in late S phase explains CFS replication features, whereas formation of sequence-dependent fork barriers or head-on transcription–replication conflicts do not. We further show that transcription inhibition during S phase, which suppresses transcription–replication encounters and prevents origin resetting, could not rescue CFS stability. Altogether, our results show that transcription-dependent suppression of initiation events delays replication of large gene bodies, committing them to instability., Common Fragile Sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Here the authors use genome-wide and single cell techniques to assess how replication timing and transcriptional activity correlate with genome stability.

Published
2019
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5. FANCD2 tunes the UPR preventing mitochondrial stress-­induced common fragile site instability

Author

Viola Nähse, Claude Saint-Ruf, Philippe Fernandes, Silvia Ravera, Enrico Cappelli, Benoit Miotto, and Valeria Naim

Subjects
Genome instability, congenital, hereditary, and neonatal diseases and abnormalities, 0303 health sciences, Chromosomal fragile site, ATF4, nutritional and metabolic diseases, Biology, Cell biology, 03 medical and health sciences, 0302 clinical medicine, Mediator, Transcription (biology), hemic and lymphatic diseases, 030220 oncology & carcinogenesis, Gene expression, Unfolded protein response, Gene, 030304 developmental biology
Abstract

Common fragile sites (CFSs) are genomic regions frequently involved in cancer-associated rearrangements. Most CFSs lie within large genes, and their instability relies on transcription- and replication-dependent mechanisms. Here, we uncover a role for the UBL5-dependent branch of the unfolded protein response pathway (UPR) in the maintenance of CFS stability. We show that genetic or pharmacological UPR activation induces CFS gene expression and concomitant relocalization of FANCD2, a master regulator of CFS stability, to CFSs. Furthermore, a genomic analysis of FANCD2 binding sites identified an enrichment for mitochondrial UPR transcriptional response elements in FANCD2 bound regions. We demonstrated that depletion of FANCD2 increases CFS gene transcription and their instability while also inducing mitochondrial dysfunction and triggering the activation of the UPR pathway. Depletion of UBL5, a mediator of the UPR, but not ATF4, reduces CFS gene expression and breakage in FANCD2-depleted cells. We thus demonstrate that FANCD2 recruitment and function at CFSs depends on transcription and UPR signaling, and in absence of transcription or UBL5, FANCD2 is dispensable for CFS stability. We propose that FANCD2 coordinates nuclear and mitochondrial activities by tuning the UPR to prevent genome instability.

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