Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1.
J Biol Chem
; 277(25): 23028-36, 2002 Jun 21.
Article
en En
| MEDLINE
| ID: mdl-11948190
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Poli(ADP-Ribosa) Polimerasas
/
Proteínas de Unión al ADN
/
Reparación del ADN
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2002
Tipo del documento:
Article
País de afiliación:
Francia