PARP3 affects the relative contribution of homologous recombination and nonhomologous end-joining pathways.

Autor:	Beck C; Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, Equipe labellisée Ligue Nationale Contre Le Cancer, UMR7242, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, BP10413, 67412 Illkirch, France francoise.dantzer@unistra.fr., Boehler C; Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, Equipe labellisée Ligue Nationale Contre Le Cancer, UMR7242, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, BP10413, 67412 Illkirch, France francoise.dantzer@unistra.fr., Guirouilh Barbat J; Université Paris Sud, CNRS UMR8200, Institut de Cancérologie Gustave-Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France., Bonnet ME; Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, Equipe labellisée Ligue Nationale Contre Le Cancer, UMR7242, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, BP10413, 67412 Illkirch, France., Illuzzi G; Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, Equipe labellisée Ligue Nationale Contre Le Cancer, UMR7242, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, BP10413, 67412 Illkirch, France., Ronde P; Laboratoire de biophotonique et pharmacologie, UMR 7213, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Faculté de pharmacie, 74 route du Rhin, 67401 Illkirch, France., Gauthier LR; CEA DSV iRCM SCSR, Laboratoire de radiopathologie, INSERM, U967, 92265 Fontenay-aux-Roses, France., Magroun N; Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, Equipe labellisée Ligue Nationale Contre Le Cancer, UMR7242, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, BP10413, 67412 Illkirch, France., Rajendran A; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA., Lopez BS; Université Paris Sud, CNRS UMR8200, Institut de Cancérologie Gustave-Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France., Scully R; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA., Boussin FD; CEA DSV iRCM SCSR, Laboratoire de radiopathologie, INSERM, U967, 92265 Fontenay-aux-Roses, France., Schreiber V; Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, Equipe labellisée Ligue Nationale Contre Le Cancer, UMR7242, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, BP10413, 67412 Illkirch, France., Dantzer F; Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, Equipe labellisée Ligue Nationale Contre Le Cancer, UMR7242, Centre Nationale de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, BP10413, 67412 Illkirch, France francoise.dantzer@unistra.fr.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2014 May; Vol. 42 (9), pp. 5616-32. Date of Electronic Publication: 2014 Mar 05.
DOI:	10.1093/nar/gku174
Abstrakt:	The repair of toxic double-strand breaks (DSB) is critical for the maintenance of genome integrity. The major mechanisms that cope with DSB are: homologous recombination (HR) and classical or alternative nonhomologous end joining (C-NHEJ versus A-EJ). Because these pathways compete for the repair of DSB, the choice of the appropriate repair pathway is pivotal. Among the mechanisms that influence this choice, deoxyribonucleic acid (DNA) end resection plays a critical role by driving cells to HR, while accurate C-NHEJ is suppressed. Furthermore, end resection promotes error-prone A-EJ. Increasing evidence define Poly(ADP-ribose) polymerase 3 (PARP3, also known as ARTD3) as an important player in cellular response to DSB. In this work, we reveal a specific feature of PARP3 that together with Ku80 limits DNA end resection and thereby helps in making the choice between HR and NHEJ pathways. PARP3 interacts with and PARylates Ku70/Ku80. The depletion of PARP3 impairs the recruitment of YFP-Ku80 to laser-induced DNA damage sites and induces an imbalance between BRCA1 and 53BP1. Both events result in compromised accurate C-NHEJ and a concomitant increase in DNA end resection. Nevertheless, HR is significantly reduced upon PARP3 silencing while the enhanced end resection causes mutagenic deletions during A-EJ. As a result, the absence of PARP3 confers hypersensitivity to anti-tumoral drugs generating DSB. (© The Author(s) 2014. Published by Oxford University Press.)
Databáze:	MEDLINE
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