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Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7303-7.

Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells.

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Ecole Supérieure de Biotechnologie de Strasbourg, UPR 9003 du Centre National de la Recherche Scientifique, "Cancérogenèse et Mutagenèse Moléculaire et Structurale", Boulevard Sébastien Brant, F-67400 Illkirch, France.


Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+: poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC] is a zinc-finger DNA-binding protein that detects specifically DNA strand breaks generated by genotoxic agents. To determine its biological function, we have inactivated both alleles by gene targeting in mice. Treatment of PARP-/- mice either by the alkylating agent N-methyl-N-nitrosourea (MNU) or by gamma-irradiation revealed an extreme sensitivity and a high genomic instability to both agents. Following whole body gamma-irradiation (8 Gy) mutant mice died rapidly from acute radiation toxicity to the small intestine. Mice-derived PARP-/- cells displayed a high sensitivity to MNU exposure: a G2/M arrest in mouse embryonic fibroblasts and a rapid apoptotic response and a p53 accumulation were observed in splenocytes. Altogether these results demonstrate that PARP is a survival factor playing an essential and positive role during DNA damage recovery.

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