Impact of tobacco-specific nitrosamine-derived DNA adducts on the efficiency and fidelity of DNA replication in human cells.

ABSTRACT: The tobacco-derived nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are known human carcinogens. Following metabolic activation, NNK and NNN can induce a number of DNA lesions, including several 4-(3-pyridyl)-4-oxobut-1-yl (POB) adducts. However, it remains unclear to what extent these lesions affect the efficiency and accuracy of DNA replication and how their replicative bypass is influenced by translesion synthesis (TLS) DNA polymerases. In this study, we investigated the effects of three stable POB DNA adducts (O²-POB-dT, O⁴-POB-dT, and O⁶-POB-dG) on the efficiency and fidelity of DNA replication in HEK293T human cells. We found that, when situated in a double-stranded plasmid,

SUBMITTER: Du H 

PROVIDER: S-EPMC6052226 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature