DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability
| العنوان: | DNA polymerase zeta contributes to heterochromatin replication to prevent genome instability |
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| المؤلفون: | Barbara Ben Yamin, Philippe Dessen, Caroline Pouvelle, Raphael Corre, Jean Charles Cadoret, Giuseppe Baldacci, Richard D. Wood, Sabine S. Lange, Sergey Nikolaev, Sarita Bhetawal, Jordane Goulas, Quentin Delacour, Emmanuelle Despras, Maria Teresa Mitjavila-Garcia, Andrey A. Yurchenko, Sana Ahmed-Seghir, Patricia Kannouche, Didier Goidin, Nathalie Droin, Junya Tomida |
| المساهمون: | Intégrité du génome et cancers (IGC), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), The University of Texas M.D. Anderson Cancer Center [Houston], Institut Gustave Roussy (IGR), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de Génomique [Gustave Roussy], Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Plateforme de Bioinformatique [Gustave Roussy], Agilent Technologies France, Hôpital Paul Brousse, Institut Jacques Monod (IJM (UMR_7592)), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), 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), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Gestionnaire, HAL Sorbonne Université 5 |
| المصدر: | EMBO Journal EMBO Journal, EMBO Press, 2021, 49, pp.8120-8134. ⟨10.15252/embj.2020104543⟩ The EMBO Journal EMBO Journal, 2021, 49, pp.8120-8134. ⟨10.15252/embj.2020104543⟩ |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Genome instability, REV3L, TLS polymerase, DNA Replication, Recombination & Repair, DNA-Directed DNA Polymerase, Epigenesis, Genetic, Mice, 0302 clinical medicine, DNA Breaks, Double-Stranded, Recombination & Repair, Cell Line, Transformed, 0303 health sciences, biology, TLS polymerase Subject Categories Chromatin, General Neuroscience, Gene Expression Regulation, Developmental, Articles, Cell biology, DNA-Binding Proteins, Histone, Signal Transduction, DNA Replication, DNA damage, Heterochromatin, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, replication timing, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, 03 medical and health sciences, Transcription & Genomics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Chromosomal Instability, Animals, Humans, Epigenetics, Molecular Biology, Embryonic Stem Cells, 030304 developmental biology, Cell Proliferation, Replication timing, General Immunology and Microbiology, DNA replication, heterochromatin, DNA, Fibroblasts, Embryo, Mammalian, Mice, Inbred C57BL, Chromobox Protein Homolog 5, Chromatin, Transcription & Genomics, biology.protein, NIH 3T3 Cells, Heterochromatin protein 1, 030217 neurology & neurosurgery, HeLa Cells |
| الوصف: | The DNA polymerase zeta (Polζ) plays a critical role in bypassing DNA damage. REV3L, the catalytic subunit of Polζ, is also essential in mouse embryonic development and cell proliferation for reasons that remain incompletely understood. In this study, we reveal that REV3L protein interacts with heterochromatin components including repressive histone marks and localizes in pericentromeric regions through direct interaction with HP1 dimer. We demonstrate that Polζ/REV3L ensures progression of replication forks through difficult‐to‐replicate pericentromeric heterochromatin, thereby preventing spontaneous chromosome break formation. We also find that Rev3l‐deficient cells are compromised in the repair of heterochromatin‐associated double‐stranded breaks, eliciting deletions in late‐replicating regions. Lack of REV3L leads to further consequences that may be ascribed to heterochromatin replication and repair‐associated functions of Polζ, with a disruption of the temporal replication program at specific loci. This is correlated with changes in epigenetic landscape and transcriptional control of developmentally regulated genes. These results reveal a new function of Polζ in preventing chromosome instability during replication of heterochromatic regions. HP1‐mediated targeting of REVL3, the catalytic subunit of translesion synthesis Polζ, influences replication fork progression and epigenetic and transcriptional landscapes of developmentally‐regulated genes. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0261-4189 1460-2075 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecceeb3ccfb8f90285de395b8fd780e8Test https://hal.sorbonne-universite.fr/hal-03353667Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ecceeb3ccfb8f90285de395b8fd780e8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02614189 14602075 |
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