Mutagenicity and genotoxicity of (5'S)-8,5'-cyclo-2'-deoxyadenosine in Escherichia coli and replication of (5'S)-8,5'-cyclopurine-2'-deoxynucleosides in vitro by DNA polymerase IV, exo-free Klenow fragment, and Dpo4.

ABSTRACT: Reactive oxygen species generate many lesions in DNA, including R and S diastereomers of 8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine (cdG). Herein, the result of replication of a plasmid containing S-cdA in Escherichia coli is reported. S-cdA was found mutagenic and highly genotoxic. Viability and mutagenicity of the S-cdA construct were dependent on functional pol V, but mutational frequencies (MFs) and types varied in pol II- and pol IV-deficient strains relative to the wild-type strain. Both S-cdA → T and S-cdA → G substitutions occurred in equal frequency in wild-type E. coli, but the frequency of S-cdA → G dropped in pol IV-deficient strain, especially when being SOS induced. This suggests that pol IV plays a role in S-cdA → G mutations. MF increased significan

SUBMITTER: Pednekar V 

PROVIDER: S-EPMC3952113 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature