Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model?

Poly (ADP-ribose) polymerase (113 kDa; PARP-1) is a constitutive factor of the DNA damage surveillance network developed by the eukaryotic cell to cop e with the numerous environmental and endogenous genotoxic agents. This enz yme recognizes and is activated by DNA strand breaks. This original propert y plays an essential role in the protection and processing of the DNA ends as they arise in DNA damage that triggers the base excision repair (BER) pa thway. The generation, by homologous recombination, of three independent de ficient mouse models have confirmed the caretaker function of PARP-1 in mam malian cells under genotoxic stress. Unexpectedly, the knockout strategy ha s revealed the instrumental role of PARP-1 in cell death after ischemia-rep erfusion injury and in various inflammation process. Moreover, the residual PARP activity found in PARP-1 deficient cells has been recently attributed to a novel DNA damage-dependent poly ADP-ribose polymerase (62 kDa; PARP-2 ), another member of the expanding PARP family that, on the whole, appears to be involved in the genome protection. The present review summarizes the recent data obtained with the three PARP knockout mice in comparison with t he chemical inhibitor approach. (C) 2000 Elsevier Science B.V. All rights r eserved.