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.
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.
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DOI：
10.1021/acs.biochem.5b00119
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发表时间：
2015-03-17
期刊：
影响因子：
2.9
通讯作者：
Basu AK
中科院分区：
文献类型：
--
作者：
Pande P;Haraguchi K;Jiang YL;Greenberg MM;Basu AK
8-OxodGuo和Fapy•dG在4种TG*N序列背景下诱导HEK 293T细胞10-22%的突变，主要是G→T转换，其中N = C， G， A， T。siRNA敲低pol λ导致8-OxodGuo构建的后代在TG*T和TG*G序列中分别增加34%和55%的突变，这表明pol λ参与了8-OxodGuo的无错误绕过。相比之下，对于Fapy•dG， G→T突变在TG*T和TG*G序列中分别减少了27%和46%，这表明pol λ对Fapy•dG诱导的G→T突变有很大一部分负责。
8-OxodGuo and Fapy•dG induced 10–22% mutations, predominantly G→T transversions, in HEK 293T cells in four TG*N sequence contexts, where N = C, G, A, or T. siRNA knockdown of pol λ resulted in a 34% and 55% increase in mutations in the progeny from the 8-oxodGuo construct in the TG*T and TG*G sequence, respectively, suggesting that pol λ is involved in error-free bypass of 8-oxodGuo. For Fapy•dG, in contrast, G→T mutations were reduced by 27% and 46%, respectively, in the TG*T and TG*G sequence, suggesting that pol λ is responsible for a significant fraction of Fapy•dG-induced G→T mutations.