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

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de Murcia, Josiane Ménissier, Niedergang, Claude, Trucco, Carlotta, Ricoul, Michèle, Dutrillaux, Bernard, Mark, Manuel, Oliver, F. Javier, Masson, Murielle, Dierich, Andrée, LeMeur, Marianne, Walztinger, Caroline, Chambon, Pierre, de Murcia, Gilbert·1997·Proceedings of the National Academy of Sciences

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 γ-irradiation revealed an extreme sensitivity and a high genomic instability to both agents. Following whole body γ-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 G 2 /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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Metadata

Authors
de Murcia, J. M., 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.
Venue
Proceedings of the National Academy of Sciences
Published
1997-07-08
Volume
94
Issue
14
Pages
7303-7307
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2156442575
Cited by
1,056
References
0
FWCI
18.00
Type
journal article
Language
en
Open access
green

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de Murcia, J. M., 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. (1997). Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.94.14.7303

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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