Lesion Orientation of O⁴-Alkylthymidine Influences Replication by Human DNA Polymerase η.

ABSTRACT: DNA lesions that elude repair may undergo translesion synthesis catalyzed by Y-family DNA polymerases. O⁴-Alkylthymidines, persistent adducts that can result from carcinogenic agents, may be encountered by DNA polymerases. The influence of lesion orientation around the C4-O⁴ bond on processing by human DNA polymerase η (hPol η) was studied for oligonucleotides containing O⁴-methylthymidine, O⁴-ethylthymidine, and analogs restricting the O⁴-methylene group in an anti-orientation. Primer extension assays revealed that the O⁴-alkyl orientation influences hPol η bypass. Crystal structures of hPol η•DNA•dNTP ternary complexes with O⁴-me

SUBMITTER: O'Flaherty DK 

PROVIDER: S-EPMC5001687 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature