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.
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.
†Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.
Paritosh
P
Pande
‡Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Kazuhiro
K
Haraguchi
‡Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Yu-Lin
YL
Jiang
‡Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Marc M
MM
Greenberg
†Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.
Ashis K
AK
Basu
D002384:Catalysis; D004247:DNA / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D019951:DNA Polymerase beta / Q000737:chemistry* / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017354:Point Mutation; D013942:Thymine Nucleotides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D013942:Thymine Nucleotides; C057674:8-hydroxyguanosine triphosphate; D006160:Guanosine Triphosphate; D004247:DNA; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta