Homologous recombination is involved in repair of chromium-induced DNA damage in mammalian cells |
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Authors: | Bryant Helen E Ying Songmin Helleday Thomas |
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Institution: | The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK. |
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Abstract: | Chromium is a potent human carcinogen, probably because of its well-documented genotoxic effects. Chromate (CrVI]) causes a wide range of DNA lesions, including DNA crosslinks and strand breaks, presumably due to the direct and indirect effects of DNA oxidation. Homologous recombination repair (HRR) is important for error-free repair of lesions occurring at replication forks. Here, we show that HR deficient cell lines irs1SF and V-C8, deficient in XRCC3 and BRCA2, respectively, are hypersensitive to CrVI], implicating this repair pathway in repair of CrVI] damage. Furthermore, we find that CrVI] causes DNA double-strand breaks and triggers both Rad51 foci formation and induction of HRR. Collectively, these data suggest that HRR is important in repair of CrVI]-induced DNA damage. In addition, we find that ERCC1, XRCC1 and DNA-PKcs defective cells are hypersensitive to CrVI], indicating that several repair pathways cooperate in repairing CrVI]-induced DNA damage. |
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