title: Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1.
abstract: The DNA damage dependence of poly(ADP-ribose) polymerase-2 (PARP-2) activity is suggestive of its implication in genome surveillance and protection. Here we show that the PARP-2 gene, mainly expressed in actively dividing tissues follows, but to a smaller extent, that of PARP-1 during mouse development. We found that PARP-2 and PARP-1 homo- and heterodimerize; the interacting interfaces, sites of reciprocal modification, have been mapped. PARP-2 was also found to interact with three other proteins involved in the base excision repair pathway: x-ray cross complementing factor 1 (XRCC1), DNA polymerase beta, and DNA ligase III, already known as partners of PARP-1. XRCC1 negatively regulates PARP-2 activity, as it does for PARP-1, while being a polymer acceptor for both PARP-1 and PARP-2. To gain insight into the physiological role of PARP-2 in response to genotoxic stress, we developed by gene disruption mice deficient in PARP-2. Following treatment by the alkylating agent N-nitroso-N-methylurea (MNU), PARP-2-deficient cells displayed an important delay in DNA strand breaks resealing, similar to that observed in PARP-1 deficient cells, thus confirming that PARP-2 is also an active player in base excision repair despite its low capacity to synthesize ADP-ribose polymers.
authors.affiliation: UPR 9003 du Centre National de la Recherche Scientifique, Laboratoire conventionné avec le Commissariat à l'Energie Atomique, Université Louis Pasteur, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Schreiber
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Amé
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.forename: Inès
authors.initials: I
authors.lastname: Schultz
authors.forename: Bruno
authors.initials: B
authors.lastname: Rinaldi
authors.forename: Valérie
authors.initials: V
authors.lastname: Fraulob
authors.forename: Josiane
authors.initials: J
authors.lastname: Ménissier-de Murcia
authors.forename: Gilbert
authors.initials: G
authors.lastname: de Murcia
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D020552:Comet Assay; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D019951:DNA Polymerase beta / Q000378:metabolism; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D008770:Methylnitrosourea / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014018:Tissue Distribution; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
chemical_list: D000477:Alkylating Agents; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D029867:Xenopus Proteins; C000619352:Xrcc1 protein, mouse; D008770:Methylnitrosourea; D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse; D005982:Glutathione Transferase; D019951:DNA Polymerase beta; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human; C000618818:Lig3 protein, mouse