Kinetics of O(6)-pyridyloxobutyl-2'-deoxyguanosine repair by human O(6)-alkylguanine DNA alkyltransferase.

ABSTRACT: Tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosonicotine (NNN) are potent carcinogens believed to contribute to the development of lung tumors in smokers. NNK and NNN are metabolized to DNA-reactive species that form a range of nucleobase adducts, including bulky O(6)-[4-oxo-4-(3-pyridyl)but-1-yl]deoxyguanosine (O(6)-POB-dG) lesions. If not repaired, O(6)-POB-dG adducts induce large numbers of G → A and G → T mutations. Previous studies have shown that O(6)-POB-dG can be directly repaired by O(6)-alkylguanine-DNA alkyltransferase (AGT), which transfers the pyridyloxobutyl group from O(6)-alkylguanines in DNA to an active site cysteine residue within the protein. In the present study, we investigated the influence of DNA sequence context and e

SUBMITTER: Kotandeniya D 

PROVIDER: S-EPMC3750081 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature