US EPA

1509338 

Journal Article 

Inhibition of nucleotide excision repair by arsenic 

Shen, S; Wang, C; Weinfeld, M; Le, XC 

2013 

Yes 

Chinese Science Bulletin
ISSN: 1001-6538
EISSN: 1861-9541 

58 

2 

214-221 

10.1007/s11434-012-5439-x 

WOS:000313793000011 

http://www.springerlink.com/index/10.1007/s11434-012-5439-x
Exit
 

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. 

arsenic; carcinogenesis; DNA repair; nucleotide excision repair; p53; nitric oxide; PARP-1; protein binding