DNA Polymerase λ Promotes Mutagenesis Induced by 8-Oxo-7,8-dihydroguanine (8-hydroxyguanine) Paired with Adenine

摘要

References(40) Cited-By(2) DNA polymerase λ preferentially inserts dCTP opposite 8-oxo-7,8-dihydroguanine (GO, 8-hydroxyguanine) in vitro, and this function is considered to be important after A base removal from GO:A pairs by the MUTYH DNA glycosylase. However, dCTP incorporation would promote A:T→C:G transversion mutations induced by 8-oxo-7,8-dihydro-dGTP (dGOTP), the mutation triggered by the incorporation of dGOTP opposite A in the template DNA. In this study, double-stranded plasmid DNA containing the GO:A pair, an intermediate in the dGOTP mutagenesis pathway, was transfected into human cells in which DNA polymerase λ was knocked down. The knockdown of DNA polymerase λ significantly reduced the frequency of A:T→C:G transversion mutations induced by the GO:A pair although the knockdown effect was small. These results suggested that DNA polymerase λ is involved in the mutagenesis processes of GO, generated by dGOTP, in the nucleotide pool.