Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1.

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.
Mesh Terms:
Alkylating Agents, Animals, Blotting, Western, Cell Survival, Comet Assay, DNA Damage, DNA Ligases, DNA Polymerase beta, DNA Repair, DNA, Complementary, DNA-Binding Proteins, Dimerization, Gene Deletion, Gene Expression Regulation, Glutathione Transferase, Hela Cells, Humans, In Situ Hybridization, Methylnitrosourea, Mice, Mutation, Plasmids, Poly(ADP-ribose) Polymerases, Protein Binding, Protein Structure, Tertiary, Time Factors, Tissue Distribution
J. Biol. Chem.
Date: Jun. 21, 2002
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