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Your search keyword '"Hülya, Kayserili"' showing total 4 results
Start Over Author "Hülya, Kayserili" Journal nature communications
4 results on '"Hülya, Kayserili"'

1. SNUPN deficiency causes a recessive muscular dystrophy due to RNA mis-splicing and ECM dysregulation

Author

Marwan Nashabat, Nasrinsadat Nabavizadeh, Hilal Pırıl Saraçoğlu, Burak Sarıbaş, Şahin Avcı, Esra Börklü, Emmanuel Beillard, Elanur Yılmaz, Seyide Ecesu Uygur, Cavit Kerem Kayhan, Luca Bosco, Zeynep Bengi Eren, Katharina Steindl, Manuela Friederike Richter, Guney Bademci, Anita Rauch, Zohreh Fattahi, Maria Lucia Valentino, Anne M. Connolly, Angela Bahr, Laura Viola, Anke Katharina Bergmann, Maria Eugenia Rocha, LeShon Peart, Derly Liseth Castro-Rojas, Eva Bültmann, Suliman Khan, Miriam Liliana Giarrana, Raluca Ioana Teleanu, Joanna Michelle Gonzalez, Antonella Pini, Ines Sophie Schädlich, Katharina Vill, Melanie Brugger, Stephan Zuchner, Andreia Pinto, Sandra Donkervoort, Stephanie Ann Bivona, Anca Riza, Undiagnosed Diseases Network, Ioana Streata, Dieter Gläser, Carolina Baquero-Montoya, Natalia Garcia-Restrepo, Urania Kotzaeridou, Theresa Brunet, Diana Anamaria Epure, Aida Bertoli-Avella, Ariana Kariminejad, Mustafa Tekin, Sandra von Hardenberg, Carsten G. Bönnemann, Georg M. Stettner, Ginevra Zanni, Hülya Kayserili, Zehra Piraye Oflazer, and Nathalie Escande-Beillard

Subjects
Science
Abstract

Abstract SNURPORTIN-1, encoded by SNUPN, plays a central role in the nuclear import of spliceosomal small nuclear ribonucleoproteins. However, its physiological function remains unexplored. In this study, we investigate 18 children from 15 unrelated families who present with atypical muscular dystrophy and neurological defects. Nine hypomorphic SNUPN biallelic variants, predominantly clustered in the last coding exon, are ascertained to segregate with the disease. We demonstrate that mutant SPN1 failed to oligomerize leading to cytoplasmic aggregation in patients’ primary fibroblasts and CRISPR/Cas9-mediated mutant cell lines. Additionally, mutant nuclei exhibit defective spliceosomal maturation and breakdown of Cajal bodies. Transcriptome analyses reveal splicing and mRNA expression dysregulation, particularly in sarcolemmal components, causing disruption of cytoskeletal organization in mutant cells and patient muscle tissues. Our findings establish SNUPN deficiency as the genetic etiology of a previously unrecognized subtype of muscular dystrophy and provide robust evidence of the role of SPN1 for muscle homeostasis.

Published
2024
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2. Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology

Author

Yulia Kargapolova, Rizwan Rehimi, Hülya Kayserili, Joanna Brühl, Konstantinos Sofiadis, Anne Zirkel, Spiros Palikyras, Athanasia Mizi, Yun Li, Gökhan Yigit, Alexander Hoischen, Stefan Frank, Nicole Russ, Jonathan Trautwein, Bregje van Bon, Christian Gilissen, Magdalena Laugsch, Eduardo Gade Gusmao, Natasa Josipovic, Janine Altmüller, Peter Nürnberg, Gernot Längst, Frank J. Kaiser, Erwan Watrin, Han Brunner, Alvaro Rada-Iglesias, Leo Kurian, Bernd Wollnik, Karim Bouazoune, and Argyris Papantonis

Subjects
Science
Abstract

Members of the CHD chromatin remodeler family are implicated in human pathologies, however CHD6 remained poorly studied. Here, the authors show that CHD6 binds to and regulates autophagy and stress response genes across cell types. They identify a clinical mutation that affects its ability to recruit cofactors, leading to impaired autophagy induction and DNA repair.

Published
2021
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3. Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology

Author

Stefan Frank, Yulia Kargapolova, Joanna Brühl, Karim Bouazoune, Rizwan Rehimi, Jonathan Trautwein, Argyris Papantonis, Bernd Wollnik, Alvaro Rada-Iglesias, Bregje W.M. van Bon, Nicole Russ, Magdalena Laugsch, Erwan Watrin, Eduardo G. Gusmao, Hülya Kayserili, Leo Kurian, Christian Gilissen, Konstantinos Sofiadis, Anne Zirkel, Frank J. Kaiser, Han G. Brunner, Gökhan Yigit, Natasa Josipovic, Alexander Hoischen, Peter Nürnberg, Janine Altmüller, Yun Li, Athanasia Mizi, Spiros Palikyras, Gernot Längst, University of Cologne, University Hospital of Cologne [Cologne], Koç University, Philipps Universität Marburg = Philipps University of Marburg, University Medical Center Göttingen (UMG), Radboud University Medical Center [Nijmegen], University of Heidelberg, Medical Faculty, University of Regensburg, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universidad de Cantabria [Santander], Georg-August-University = Georg-August-Universität Göttingen, Deutsche Forschungsgemeinschaft, DFG: 109546710, 2015_A125, 360043781, 397484323, CCRC2407, TRR259, Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und Molekulare Biowissenschaften, GGNB, Uniklinikum Giessen und Marburg, UKGM: 5/2016, Open Access funding enabled and organized by Projekt DEAL., Philipps University of Marburg, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of Göttingen - Georg-August-Universität Göttingen, German Research Foundation, International Max Planck Research Schools, Projekt DEAL, Karabey Kayserili, Hülya (ORCID 0000-0003-0376-499X & YÖK ID 7945), Kargapolova, Yulia, Rehimi, Rizwan, Bruehl, Joanna, Sofiadis, Konstantinos, Zirkel, Anne, Palikyras, Spiros, Mizi, Athanasia, Li, Yun, Yigit, Gokhan, Hoischen, Alexander, Frank, Stefan, Russ, Nicole, Trautwein, Jonathan, van Bon, Bregje, Gilissen, Christian, Laugsch, Magdalena, Gusmao, Eduardo Gade, Josipovic, Natasa, Altmueller, Janine, Nuernberg, Peter, Laengst, Gernot, Kaiser, Frank J., Watrin, Erwan, Brunner, Han, Rada-Iglesias, Alvaro, Kurian, Leo, Wollnik, Bernd, Bouazoune, Karim, Papantonis, Argyris, and School of Medicine

Subjects
0301 basic medicine, Epigenomics, [SDV]Life Sciences [q-bio], Hallermann Streiff syndrome, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Medizin, General Physics and Astronomy, Gene Expression, nerve protein, medicine.disease_cause, CHD6 protein, 0302 clinical medicine, Missense mutation, genetics, Science and technology, Gene Editing, Mutation, Multidisciplinary, integumentary system, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Genomics, Chromatin, 3. Good health, Cell biology, enzyme activity, DNA-Binding Proteins, Technology Platforms, autophagy, Protein family, DNA damage, phenotype, Science, Protein structure, Binding domain, Mutations, Gene, Stress, PBAF, Translocation, Phenotypes, SMARCB1, DNA helicase, Nerve Tissue Proteins, Biology, chromatin assembly and disassembly, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Autophagy, genomics, Humans, human, Hallermann's Syndrome, chemical binding, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], epigenetics, DNA Helicases, General Chemistry, DNA, DNA binding protein, 030104 developmental biology, physiology, pathology, protein, metabolism, 030217 neurology & neurosurgery
Abstract

© The Author(s) 2021., Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. By combining genomics with functional in vivo and in vitro assays, we show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS mutation affects CHD6 protein folding and impairs its ability to recruit co-remodelers in response to DNA damage or autophagy stimulation. This leads to accumulation of DNA damage burden and senescence-like phenotypes. We therefore uncovered a molecular mechanism explaining HSS onset via chromatin control of autophagic flux and genotoxic stress surveillance., This work was supported by UKGM (Project 5/2016), by the Deutsche Forschungsgemeinschaft via TRR81 (Project 109546710) and CCRC2407 (Project 360043781), as well as by an Else-Kroener-Fresenius-Stiftung “Key-Project” grant (Project 2015_A125). Y.K. was further supported by the TRR259 (Project 397484323), and S.P. and N.J. by the International Max Planck Research School for Genome Science, part of the GAUSS/GGNB. Open Access funding enabled and organized by Projekt DEAL.

Published
2021
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4. De novo mutations in PLXND1 and REV3L cause Möbius syndrome

Author

Tony Roscioli, Arturo Carta, Jacob G. Jansen, Han G. Brunner, Christian Gilissen, Dirk Schubert, Zafar Iqbal, Manvendra K. Singh, Harriëtte T.F.M. Verzijl, Antonio Perez Aytes, Hülya Kayserili, George W. Padberg, Arjan P.M. de Brouwer, Faustino Marín, Pilar Aroca, Corrie E. Erasmus, Hans van Bokhoven, Umut Altunoglu, Laura Soria, Jonathan A. Epstein, Anastasia Tsaalbi-Shtylik, Ellen van Beusekom, Niels de Wind, Alexander Hoischen, Laura Tomás-Roca, Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB,The Netherlands., Department of Human Anatomy and Psychobiology, School of Medicine, University of Murcia, 30100 Espinardo (Murcia), Spain., Department of Human Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands., Department of Cell andDevelopmental Biology, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 9-105 SCTR, 3400 Civic Center Boulevard,Philadelphia, Pennsylvania 19104, USA, Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical SchoolSingapore, National Heart Center Singapore, 8 College Road, Singapore 169857, Singapore, Medical Genetics Department, Istanbul Medical Faculty,Istanbul University, Millet Caddesi, Capa, Fatih 34093, Turkey., Department of Neurology, Radboud University Medical Center, Donders Institute for Brain,Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands., The Kinghorn Centre for Clinical Genomics, Garvan Institute of MedicalResearch, Sydney, New South Wales 2010, Australia, Department of Human Genetics, Radboud University Medical Center, Radboud Institute for MolecularLife Sciences (RIMLS), PO Box 9101, Nijmegen 6500 HB, The Netherlands., Department of Cognitive Neuroscience, Radboud University Medical Center,Donders Institute for Brain, Cognition and Behaviour, PO Box 9101, Nijmegen 6500 HB, The Netherlands, Department of Clinical Genetics, MaastrichtUniversity Medical Center, PO Box 5800, Maastricht 6200AZ, The Netherlands., Dysmorphology and Reproductive Genetics Unit, Moebius SyndromeFoundation of Spain, University Hospital LA FE, Valencia 46540, Spain., Ophthalmology Unit, Department of Biomedical, Biotechnological and TranslationalSciences (S.Bi.Bi.T.), University of Parma, via Gramsci 14, 43126, Parma, Italy, Karabey, Hülya Kayserili (ORCID 0000-0003-0376-499X & YÖK ID 7945), Tomas-Roca, Laura, Tsaalbi-Shtylik, Anastasia, Jansen, Jacob G., Singh, Manvendra K., Epstein, Jonathan A., Altunoglu, Umut, Verzijl, Harriette, Soria, Laura, van Beusekom, Ellen, Roscioli, Tony, Iqbal, Zafar, Gilissen, Christian, Hoischen, Alexander, de Brouwer,Arjan P. M., Erasmus, Corrie, Schubert, Dirk, Brunner, Han, Aytes, Antonio Perez, Marin, Faustino, Aroca, Pilar, Carta, Arturo, de Wind, Niels, Padberg, George W., van Bokhoven, Hans, School of Medicine, and Department of Medical Genetics

Subjects
Möbius syndrome, REV3L, Heterozygote, animal structures, DNA damage, Cell Adhesion Molecules, Neuronal, Moebius syndrome, Dna-damage, Vascular etiology, Syndrome variant, Dutch family, Gene, Sequence, Humans, Cells, Mechanisms, Neurophysiology, Other Research Donders Center for Medical Neuroscience [Radboudumc 0], General Physics and Astronomy, Hindbrain, DNA-Directed DNA Polymerase, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Article, Mice, medicine, Animals, Exome, PLXND1, Genetics, Mutation, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Multidisciplinary, Membrane Glycoproteins, Intracellular Signaling Peptides and Proteins, Heterozygote advantage, General Chemistry, medicine.disease, Mice, Mutant Strains, Mobius Syndrome, DNA-Binding Proteins, Mobius syndrome, Multidisciplinary sciences, Molecular biology and genetics, 5 - Ciencias puras y naturales [CDU], DNA Damage
Abstract

Mobius syndrome (MBS) is a neurological disorder that is characterized by paralysis of the facial nerves and variable other congenital anomalies. The aetiology of this syndrome has been enigmatic since the initial descriptions by von Graefe in 1880 and by Mobius in 1888, and it has been debated for decades whether MBS has a genetic or a non-genetic aetiology. Here, we report de novo mutations affecting two genes, PLXND1 and REV3L in MBS patients. PLXND1 and REV3L represent totally unrelated pathways involved in hindbrain development: neural migration and DNA translesion synthesis, essential for the replication of endogenously damaged DNA, respectively. Interestingly, analysis of Plxnd1 and Rev3l mutant mice shows that disruption of these separate pathways converge at the facial branchiomotor nucleus, affecting either motoneuron migration or proliferation. The finding that PLXND1 and REV3L mutations are responsible for a proportion of MBS patients suggests that de novo mutations in other genes might account for other MBS patients., Fundacion Seneca fellowship; EMBO short-term fellowship; IBRO Project InEurope grants programme; Fundacion Cultural Privada Esteban-Romero; European Union FP7 Large-Scale Integrating Project Genetic and Epigenetic Networks in Cognitive Dysfunction; Scientific and Technological Research Council of Turkey (TÜBİTAK); CRANIRARE consortia of the European Research Area Network (E-RARE); Italian Association of Mobius Syndrome (AISMO); Dutch Cancer Society; Netherlands Organization for Health Research and Development

Published
2015

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