PARP2 controls double-strand break repair pathway choice by limiting 53BP1 accumulation at DNA damage sites and promoting end-resection
| Autor: | Janet Hall, Bernard S. Lopez, Josée Guirouilh-Barbat, Alexis Fouquin, Vincent Pennaneach, Mounira Amor-Guéret |
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| Přispěvatelé: | Stress génotoxiques et cancer, Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Paris-Sud - Paris 11 (UP11), Stabilité Génétique et Oncogenèse (UMR 8200), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institute of Terrestrial Ecology, Monks Wood, Génotoxicologie, signalisation et radiothérapie expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
DNA End-Joining Repair DNA Repair DNA repair DNA damage [SDV]Life Sciences [q-bio] MESH: DNA Breaks Double-Stranded MESH: Carrier Proteins [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC]Life Sciences [q-bio]/Cellular Biology Genome Integrity Repair and Replication Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics Humans DNA Breaks Double-Stranded Endodeoxyribonucleases ComputingMilieux_MISCELLANEOUS Polymerase MESH: BRCA1 Protein MESH: DNA Repair MESH: Humans biology BRCA1 Protein MESH: Poly(ADP-ribose) Polymerases Nuclear Proteins Recombinational DNA Repair MESH: DNA End-Joining Repair Double Strand Break Repair Cell biology MESH: Cell Line MESH: Recombinational DNA Repair 030104 developmental biology chemistry [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics 030220 oncology & carcinogenesis MESH: Tumor Suppressor p53-Binding Protein 1 biology.protein Poly(ADP-ribose) Polymerases Carrier Proteins Tumor Suppressor p53-Binding Protein 1 Homologous recombination MESH: Nuclear Proteins DNA |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2017, 45 (21), pp.12325-12339. ⟨10.1093/nar/gkx881⟩ |
| ISSN: | 0305-1048 1362-4962 |
| DOI: | 10.1093/nar/gkx881⟩ |
| Popis: | International audience; Double strand breaks (DSBs) are one of the most toxic lesions to cells. DSB repair by the canonical non-homologous end-joining (C-EJ) pathway involves minor, if any, processing of the broken DNA-ends, whereas the initiation of DNA resection channels the broken-ends toward DNA repair pathways using various lengths of homology. Mechanisms that control the resection initiation are thus central to the regulation to the choice of DSB repair pathway. Therefore, understanding the mechanisms which regulate the initiation of DNA end-resection is of prime importance. Our findings reveal that poly(ADP-ribose) polymerase 2 (PARP2) is involved in DSBR pathway choice independently of its PAR synthesis activity. We show that PARP2 favors repair by homologous recombination (HR), single strand annealing (SSA) and alternative-end joining (A-EJ) rather than the C-EJ pathway and increases the deletion sizes at A-EJ junctions. We demonstrate that PARP2 specifically limits the accumulation of the resection barrier factor 53BP1 at DNA damage sites, allowing efficient CtIP-dependent DNA end-resection. Collectively, we have identified a new PARP2 function, independent of its PAR synthesis activity, which directs DSBs toward resection-dependent repair pathways. |
| Databáze: | OpenAIRE |
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