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Title: 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.

Authors: Pande, Paritosh; Haraguchi, Kazuhiro; Jiang, Yu-Lin; Greenberg, Marc M; Basu, Ashis K

Published In Biochemistry, (2015 Mar 17)

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.

PubMed ID: 25741586 Exiting the NIEHS site

MeSH Terms: Catalysis; DNA Polymerase beta/chemistry*; DNA Polymerase beta/metabolism; DNA/biosynthesis; DNA/chemistry*; DNA/genetics; Guanosine Triphosphate/analogs & derivatives*; Guanosine Triphosphate/chemistry; Guanosine Triphosphate/genetics; Guanosine Triphosphate/metabolism; Humans; Point Mutation*; Thymine Nucleotides/chemistry*; Thymine Nucleotides/genetics; Thymine Nucleotides/metabolism

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