Inhibition of nucleotide excision repair by arsenic  

作　　者：SHEN Shengwen WANG Chuan WEINFELD Michael LE X Chris 

机构地区：[1]Department of Laboratory Medicine and Pathology [2]Cross Cancer Institute,University of Alberta

出　　处：《Chinese Science Bulletin》2013年第2期214-221,共8页

基　　金：supported by the Canadian Institutes of Health Research;the Natural Sciences and Engineering Research Council of Canada;the Canada Research Chairs Program;Alberta Health and Wellness,Alberta Cancer Foundation;Alberta Innovates Energy and Environment Solutions

摘　　要：Inhibition of DNA repair is one proposed mechanism for the co-mutagenicity/co-carcinogenicity of arsenic.This review summarizes the current literature on the effects of arsenic compounds on nucleotide excision repair(NER).Several possible mechanisms for the observed NER inhibition have been proposed.Modulation of the expression of NER proteins has been considered to be one possibility of impairing the NER process.However,data on the effects of arsenic on the expression of NER proteins remain inconsistent.It is more likely that arsenic inhibits the induction of accessory or other key proteins involved in cellular control of DNA repair pathways,such as p53.For example,arsenic affects p53 phosphorylation and p53 DNA binding activity,which could regulate NER through transcriptional activation of downstream NER genes.Although it is important to study possible direct inactivation of NER proteins by arsenic binding,indirect inactivation of proteins having thiol residues critical to their function or zinc finger proteins cannot be negated.For example,nitric oxide(NO) induced in arsenic-treated cells serves as a specific inhibitor of NER,possibly through NO-induced S-nitrosylation of proteins related to DNA repair.Poly(ADP-ribose) polymerase-1,a zinc finger protein implicated in both NER and base excision repair(BER),deserves special attention because of its involvement in NO production and its broad range of protein substrates including many repair enzymes.Inhibition of DNA repair is one proposed mechanism for the co-mutagenicity/co-carcinogenicity of arsenic. This review summa- rizes the current literature on the effects of arsenic compounds on nucleotide excision repair （NER）. Several possible mechanisms for the observed NER inhibition have been proposed. Modulation of the expression of NER proteins has been considered to be one possibility of impairing the NER process. However, data on the effects of arsenic on the expression of NER proteins remain inconsistent. It is more likely that arsenic inhibits the induction of accessory or other key proteins involved in cellular control of DNA repair pathways, such as p53. For example, arsenic affects p53 phosphorylation and p53 DNA binding activity, which could regulate NER through transcriptional activation of downstream NER genes. Although it is important to study possible direct inac- tivation of NER proteins by arsenic binding, indirect inactivation of proteins having thiol residues critical to their function or zinc finger proteins cannot be negated. For example, nitric oxide （NO） induced in arsenic-treated cells serves as a specific inhibitor of NER, possibly through NO-induced S-nitrosylation of proteins related to DNA repair. Poly（ADP-ribose） polymerase-l, a zinc finger protein implicated in both NER and base excision repair （BER）, deserves special attention because of its involvement in NO production and its broad range of protein substrates including many repair enzymes.

关 键 词：核苷酸切除修复 砷化合物 DNA修复 DNA结合活性 碱基切除修复 锌指蛋白 蛋白质 p53 

分 类 号：X13[环境科学与工程—环境科学]