砷诱导DNA修复破坏的分子机制
Molecular Mechanisms of Arsenic-Induced Disruption of DNA Repair.
作者信息
Tam Lok Ming, Price Nathan E, Wang Yinsheng
出版信息
Chem Res Toxicol. 2020 Mar 16;33(3):709-726. doi: 10.1021/acs.chemrestox.9b00464. Epub 2020 Feb 7.
Abstract
Exposure to arsenic in contaminated drinking water is an emerging public health problem that impacts more than 200 million people worldwide. Accumulating lines of evidence from epidemiological studies revealed that chronic exposure to arsenic can result in various human diseases including cancer, type 2 diabetes, and neurodegenerative disorders. Arsenic is also classified as a Group I human carcinogen. In this review, we survey extensively different modes of action for arsenic-induced carcinogenesis, with focus being placed on arsenic-mediated impairment of DNA repair pathways. Inorganic arsenic can be bioactivated by methylation, and the ensuing products are highly genotoxic. Bioactivation of arsenicals also elicits the production of reactive oxygen and nitrogen species (ROS and RNS), which can directly damage DNA and modify cysteine residues in proteins. Results from recent studies suggest zinc finger proteins as crucial molecular targets for direct binding to As or for modifications by arsenic-induced ROS/RNS, which may constitute a common mechanism underlying arsenic-induced perturbations of DNA repair.
摘要
饮用受污染的水中的砷暴露是一个新出现的公共卫生问题，影响着全球超过2亿人。流行病学研究积累的一系列证据表明，长期接触砷会导致包括癌症、2型糖尿病和神经退行性疾病在内的各种人类疾病。砷也被归类为I类人类致癌物。在本综述中，我们广泛调查了砷诱导致癌作用的不同作用模式，重点关注砷介导的DNA修复途径损伤。无机砷可通过甲基化进行生物活化，其后续产物具有高度的遗传毒性。砷化合物的生物活化还会引发活性氧和氮物种（ROS和RNS）的产生，它们可直接损伤DNA并修饰蛋白质中的半胱氨酸残基。最近的研究结果表明，锌指蛋白是直接结合砷或被砷诱导的ROS/RNS修饰的关键分子靶点，这可能构成砷诱导DNA修复紊乱的共同机制。
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本文引用的文献
1
MORC2 regulates DNA damage response through a PARP1-dependent pathway.MORC2 通过依赖 PARP1 的途径调节 DNA 损伤反应。
Nucleic Acids Res. 2019 Sep 19;47(16):8502-8520. doi: 10.1093/nar/gkz545.
2
CTCF cooperates with CtIP to drive homologous recombination repair of double-strand breaks.CTCF 与 CtIP 合作驱动双链断裂的同源重组修复。
Nucleic Acids Res. 2019 Sep 26;47(17):9160-9179. doi: 10.1093/nar/gkz639.
3
Peroxynitrite contributes to arsenic-induced PARP-1 inhibition through ROS/RNS generation.过氧亚硝酸盐通过 ROS/RNS 的产生导致砷诱导的 PARP-1 抑制。
Toxicol Appl Pharmacol. 2019 Sep 1;378:114602. doi: 10.1016/j.taap.2019.114602. Epub 2019 May 29.
4
Direct Zinc Finger Protein Persulfidation by H S Is Facilitated by Zn.HS 促进直接锌指蛋白过硫化
Angew Chem Int Ed Engl. 2019 Jun 11;58(24):7997-8001. doi: 10.1002/anie.201900823. Epub 2019 May 8.
5
Chronic low dose arsenic exposure preferentially perturbs mitotic phase of the cell cycle.长期低剂量砷暴露优先扰乱细胞周期的有丝分裂期。
Genes Cancer. 2019 Feb;10(1-2):39-51. doi: 10.18632/genesandcancer.185.
6
Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs.顺铂诱导的抗癌药物在小鼠器官中 DNA 加合物的差异损伤与修复。
Nat Commun. 2019 Jan 18;10(1):309. doi: 10.1038/s41467-019-08290-2.
7
Replication protein A (RPA) sumoylation positively influences the DNA damage checkpoint response in yeast.复制蛋白 A（RPA）的 SUMO 化正向影响酵母中的 DNA 损伤检查点反应。
J Biol Chem. 2019 Feb 22;294(8):2690-2699. doi: 10.1074/jbc.RA118.006006. Epub 2018 Dec 27.
8
RNF126 Quenches RNF168 Function in the DNA Damage Response.RNF126 可使 DNA 损伤反应中的 RNF168 失活。
Genomics Proteomics Bioinformatics. 2018 Dec;16(6):428-438. doi: 10.1016/j.gpb.2018.07.004. Epub 2018 Dec 4.
9
RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair.RNF169 限制 DSB 处 53BP1 的沉积以促进单链退火修复。
Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):E8286-E8295. doi: 10.1073/pnas.1804823115. Epub 2018 Aug 13.
10
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