Unlike Catalyzing Error-Free Bypass of 8‑OxodGuo, DNA Polymerase λ Is Responsible for a Significant Part of Fapy·dG-Induced G → T Mutations in Human Cells

Abstract

8-OxodGuo and Fapy·dG induced 10–22% mutations, predominantly G → T transversions, in human embryonic kidney 293T cells in four TG*N sequence contexts, where N = C, G, A, or T. siRNA knockdown of pol λ resulted in 34 and 55% increases in the level of mutations in the progeny from the 8-oxodGuo construct in the TG*T and TG*G sequences, respectively, suggesting that pol λ is involved in error-free bypass of 8-oxodGuo. For Fapy·dG, in contrast, the level of G → T mutations was reduced by 27 and 46% in the TG*T and TG*G sequences, respectively, suggesting that pol λ is responsible for a significant fraction of Fapy·dG-induced G → T mutations