Homologous recombination is involved in repair of chromium-induced DNA damage in mammalian cells.
Chromium is a potent human carcinogen, probably because of its well-documented genotoxic effects. Chromate (Cr[VI]) 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 Cr[VI], implicating this repair pathway in repair of Cr[VI] damage. Furthermore, we find that Cr[VI] 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 Cr[VI]-induced DNA damage. In addition, we find that ERCC1, XRCC1 and DNA-PKcs defective cells are hypersensitive to Cr[VI], indicating that several repair pathways cooperate in repairing Cr[VI]-induced DNA damage.
The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Helen E
HE
Bryant
Songmin
S
Ying
Thomas
T
Helleday
D000818:Animals; D002460:Cell Line; D002857:Chromium / Q000633:toxicity*; D019457:Chromosome Breakage; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004720:Endonucleases / Q000172:deficiency / Q000235:genetics; D005838:Genotype; D008954:Models, Biological; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D002857:Chromium; D051135:Rad51 Recombinase; D004720:Endonucleases