Portal de Periódicos da CAPES

PARP-1, PARP-2 and ATM in the DNA damage response: functional synergy in mouse development

2004; Elsevier BV; Volume: 3; Issue: 8-9 Linguagem: Inglês

10.1016/j.dnarep.2004.06.002

1568-7864

Aline Huber, Péter Bai, Josiane Ménissier de Murcia, Gilbert de Murcia,

Cell death mechanisms and regulation

Poly(ADP-ribosyl)ation is an immediate DNA damage-dependent posttranslational modification of histones and nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP-ribose) polymerases (PARPs) now constitute a superfamily of 18 proteins, encoded by different genes and displaying a common conserved catalytic domain. PARP-1 (113kDa), the founding member, and PARP-2 (62kDa) are both involved in DNA-break sensing and signaling when single strand break repair (SSBR) or base excision repair (BER) pathways are engaged. The generation by homologous recombination of deficient mouse models have confirmed the caretaker function of PARP-1 and PARP-2 in mammalian cells under genotoxic stress. This review summarizes our present knowledge on their physiological role in the cellular response to DNA damage and on the genetic interactions between PARP-1, PARP-2, Atm that play an essential role during early embryogenesis.