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Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells
Open accessAbstract
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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Citations
Cited by
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
Bryant, H. E., Schultz, N., Thomas, H. D., Parker, K. M., Flower, D., Lopez, E., Kyle, S., Meuth, M., Curtin, N. J., & Helleday, T. (2005) · Nature · doi:10.1038/nature03443 · Cited by 5,198
The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
Ray Chaudhuri, A., & Nussenzweig, A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.53 · Cited by 1,786
Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health
Cervenka, I., Agudelo, L. Z., & Ruas, J. L. (2017) · Science · doi:10.1126/science.aaf9794 · Cited by 1,382
PARP inhibition: PARP1 and beyond
Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H., & Poirier, G. G. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2812 · Cited by 1,298
Krokan, H. E., & Bjoras, M. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012583 · Cited by 1,322
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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