Inhibitory effect of uranyl nitrate on DNA double-strand break repair by depression of a set of proteins in the homologous recombination pathway
Inhibitory effect of uranyl nitrate on DNA double-strand break repair by depression of a set of proteins in the homologous recombination pathway
复制标题
硝酸铀酰通过抑制同源重组途径中的一组蛋白质对 DNA 双链断裂修复的抑制作用
DOI：
10.1039/c7tx00125h
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发表时间：
2017
影响因子：
2.1
通讯作者：
Ping-Kun Zhou
中科院分区：
文献类型：
--
作者：
Feng Jin;Teng Ma;Hua Guan;Zhi-Hua Yang;Xiao-Dan Liu;Yu Wang;Yi-Guo Jiang;Ping-Kun Zhou
已证实职业和环境接触铀会造成组织损伤和致癌作用。铀作为锕系重金属，其化学毒性和放射性毒性共同作用，对人体健康产生危害。但两种形式毒性的相互作用和机制仍需进一步阐明。DNA双链断裂（DSB）是电离辐射诱导细胞死亡或基因组不稳定的根本原因。本文从化学毒性的角度探讨硝酸铀酰对细胞DNA损伤反应和内源性DSB修复功能的影响。结果表明，铀酰离子以剂量依赖的方式增加核DNA双链断裂的积累。DSB修复的同源重组（HR）和非同源末端连接（NHEJ）途径都受到铀酰离子的影响。DSB修复效率的抑制归因于一组关键修复蛋白的抑制，特别是HR途径的那些，如ATM、BRCA 1、RPA 80和EXO 1。现有的数据使我们能够想象，铀的化学毒性导致细胞DNA修复能力受到抑制，这可能进一步加剧其放射性毒性。
Occupational and environmental exposure to uranium has been confirmed to cause tissue injury and carcinogenesis. As a heavy metal from actinide series, the chemical and radiological toxicities of uranium jointly induce the detrimental effects. However, the mutual action and mechanism of both forms of toxicities still need to be further elucidated. DNA double-strand break (DSB) is a fundamental cause of cell death or genomic instability induced by ionizing radiation. Herein, we investigate the effect of uranyl nitrate on the cellular function of DNA damage response and intrinsic DSB repair on the aspect of chemical toxicity. The results indicated that uranyl ion increased the accumulation of nuclear DNA DSBs in a dose-dependent manner. Both homologous recombination (HR) and non-homologous end joining (NHEJ) pathways of DSB repair were affected by the uranyl ion. The inhibition of DSB repair efficiency is attributed to the depression of a set of critical repair proteins, particularly those for the HR pathway such as ATM, BRCA1, RPA80 and EXO1. The available data enable us to imagine that the chemical toxicity of uranium leads to inhibition of cellular DNA repair capability, which can further aggravate its radiological toxicity.