Lesion orientation of O4-alkylthymidine influences replication by human DNA polymerase η

Abstract

Conformation of the α-carbon of O⁴-alkylthymidine was shown to exert an influence on human DNA polymerase η (hPol η) bypass. Crystal structures of hPol η·DNA·dNTP ternary complexes reveal a unique conformation adopted by O⁴-methylthymidine, where the nucleobase resides nestled at the active site ceiling where hydrogen-bonding with the incoming nucleotide is prevented.