Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination

2003 Nucleic Acids Research 292 citations

Abstract

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.

Keywords

RAD51BiologyPoly ADP ribose polymeraseHomologous recombinationPARP inhibitorMolecular biologyDNA repairDNA damageSister chromatidsDNAPolymeraseGeneticsGene

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Year
2003
Type
article
Volume
31
Issue
17
Pages
4959-4964
Citations
292
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Nikolaus Schultz (2003). Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination. Nucleic Acids Research , 31 (17) , 4959-4964. https://doi.org/10.1093/nar/gkg703

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DOI
10.1093/nar/gkg703