Poly(ADP‐ribose) polymerase (PARP‐1) has a controlling role in homologous recombination
Cells with non‐functional poly(ADP‐ribose) polymerase (PARP‐1) show increased levels of sister chromatid exchange, suggesting a hyper recombination phenotype in these cells. To further investigate the involvement of PARP‐1 in homologous recombination (HR) we investigated how PARP‐1 affects nuclear H...
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Published in | Nucleic acids research Vol. 31; no. 17; pp. 4959 - 4964 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
01.09.2003
Oxford Publishing Limited (England) |
Subjects | |
Online Access | Get full text |
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Summary: | Cells with non‐functional poly(ADP‐ribose) polymerase (PARP‐1) show increased levels of sister chromatid exchange, suggesting a hyper recombination phenotype in these cells. To further investigate the involvement of PARP‐1 in homologous recombination (HR) we investigated how PARP‐1 affects nuclear HR sites (Rad51 foci) and HR repair of an endonuclease‐induced DNA double‐strand break (DSB). Several proteins involved in HR localise to Rad51 foci and HR‐deficient cells fail to form Rad51 foci in response to DNA damage. Here, we show that PARP‐1 mainly does not localise to Rad51 foci and that Rad51 foci form in PARP‐1–/– cells, also in response to hydroxyurea. Furthermore, we show that homology directed repair following induction of a site‐specific DSB is normal in PARP‐1‐inhibited cells. In contrast, inhibition or loss of PARP‐1 increases spontaneous Rad51 foci formation, confirming a hyper recombination phenotype in these cells. Our data suggest that PARP‐1 controls DNA damage recognised by HR and that it is not involved in executing HR as such. |
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Bibliography: | ark:/67375/HXZ-1VH4FP59-S local:gkg703 Received June 16, 2003; Accepted July 8, 2003 istex:A0CF2C111E4F2D4B1B3AEA641F1357BE49FED60B To whom correspondence should be addressed at The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK. Tel: +44 114 271 2993; Fax: +44 114 271 3515; Email: t.helleday@sheffield.ac.uk Present address: Elena Lopez, Department of Molecular and Cellular Biology, IMIM, 08003 Barcelona, Spain ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Present address: Elena Lopez, Department of Molecular and Cellular Biology, IMIM, 08003 Barcelona, Spain To whom correspondence should be addressed at The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK. Tel: +44 114 271 2993; Fax: +44 114 271 3515; Email: t.helleday@sheffield.ac.uk |
ISSN: | 0305-1048 1362-4962 1362-4962 |
DOI: | 10.1093/nar/gkg703 |