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PMID: 9207086 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 14 ·1997-07-08 ·Pages 7303-7

de Murcia JM, Niedergang C, Trucco C, Ricoul M, Dutrillaux B, Mark M, Oliver FJ, Masson M, Dierich A, LeMeur M, Walztinger C, Chambon P, de Murcia G

Abstract

Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+: poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] 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.

MeSH Terms
Alleles Animals Apoptosis/physiology Cell Cycle/physiology Cells, Cultured DNA Damage Female Fibroblasts Gene Targeting Mice Mutation Poly(ADP-ribose) Polymerases/physiology Pregnancy
Chemicals
Poly(ADP-ribose) Polymerases
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
de Murcia J M
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.
Niedergang C
Trucco C
Ricoul M
Dutrillaux B
Mark M
Oliver F J
Masson M
Dierich A
LeMeur M
Walztinger C
Chambon P
de Murcia G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.14.7303
Published
1997-07-08
Pages
7303-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23816
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.14.7303 PMC Full Text View journal details
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