Expanding functions of ADP-ribosylation in the maintenance of genome integrity.
Cell response to genotoxic stress requires a complex network of sensors and effectors from numerous signaling and repair pathways, among them the nuclear poly(ADP-ribose) polymerase 1 (PARP1) plays a central role. PARP1 is catalytically activated in the setting of DNA breaks. It uses NAD+as a donor and catalyses the synthesis and subsequent covalent attachment of branched ADP-ribose polymers onto itself and various acceptor proteins to promote repair. Its inhibition is now considered as an efficient therapeutic strategy to potentiate the cytotoxic effect of chemotherapy and radiation or to exploit synthetic lethality in tumours with defective homologous recombination mediated repair. Still, efforts made on understanding the role of PARylation in DNA repair continues to yield novel discoveries. Over the last years, our knowledge in this field has been particularly advanced by the discovery of novel biochemical and functional properties featuring PARP1, by the characterization of the other PARP family members and by the identification of a panel of enzymes capable of erasing poly(ADP-ribose). The aim of this review is to provide an overview of these newest findings and their relevance in genome surveillance.
Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, UMR7242, Centre National de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, CS10413, 67412 Illkirch, France.
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Martin-Hernandez
Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, UMR7242, Centre National de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, CS10413, 67412 Illkirch, France.
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Rodriguez-Vargas
Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, UMR7242, Centre National de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, CS10413, 67412 Illkirch, France.
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Schreiber
Poly(ADP-ribosyl)ation and Genome Integrity, Laboratoire d'Excellence Medalis, UMR7242, Centre National de la Recherche Scientifique/Université de Strasbourg, Institut de Recherche de l'Ecole de Biotechnologie de Strasbourg, 300 bld. S. Brant, CS10413, 67412 Illkirch, France. Electronic address: francoise.dantzer@unistra.fr.
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Dantzer
D000074744:ADP-Ribosylation; D000818:Animals; D055162:Biocatalysis; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D016678:Genome; D006801:Humans; D008954:Models, Biological