Homologous recombination is involved in repair of chromium-induced DNA damage in mammalian cells
Homologous recombination is involved in repair of chromium-induced DNA damage in mammalian cells
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DOI：
10.1016/j.mrfmmm.2006.02.001
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发表时间：
2006-07-25
影响因子：
2.3
通讯作者：
Helleday, Thomas
中科院分区：
文献类型：
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作者：
Bryant, Helen E.;Ying, Songmin;Helleday, Thomas
铬是一种强有力的人类致癌物，可能是因为它有充分证据证明的基因毒性作用。铬酸盐（Cr[VI]）引起广泛的DNA损伤，包括DNA交联和链断裂，可能是由于DNA氧化的直接和间接影响。同源重组修复（HRR）是发生在复制叉上的病变无错误修复的重要手段。在这里，我们发现，分别缺乏XRCC3和BRCA2的HR缺陷细胞系irs1SF和V-C8对Cr[VI]过敏，暗示这一修复途径参与了Cr[VI]损伤的修复。此外，我们发现Cr[VI]引起DNA双链断裂，并触发Rad51病灶的形成和HRR的诱导。总的来说，这些数据表明HRR在修复Cr[VI]诱导的DNA损伤中很重要。此外，我们发现ERCC 1、XRCC1和DNA- pkcs缺陷细胞对Cr[VI]异常敏感，表明多种修复途径协同修复Cr[VI]诱导的DNA损伤。(c) 2006 Elsevier B.V.版权所有
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 ERCC 1, XRCC1 and DNA-PKcs defective cells are hypersensitive to Cr[VI], indicating that several repair pathways cooperate in repairing Cr[VI]-induced DNA damage. (c) 2006 Elsevier B.V. All rights reserved.