Mechanisms of accurate translesion synthesis by human DNA polymerase η

被引:433
作者
Masutani, C
Kusumoto, R
Iwai, S
Hanaoka, F
机构
[1] Osaka Univ, Inst Mol & Cellular Biol, Suita, Osaka 5650871, Japan
[2] Japan Sci & Technol Corp, CREST, Suita, Osaka 5650871, Japan
[3] Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan
[4] Biomol Engn Res Inst, Osaka 5650874, Japan
[5] RIKEN, Wako, Saitama 3510198, Japan
关键词
DNA polymerase eta; translesion synthesis; xeroderma pigmentosum variant (XP-V);
D O I
10.1093/emboj/19.12.3100
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta (pol eta), which is involved in the replication of damaged DNA, Pol eta catalyzes efficient and accurate translesion synthesis past cis-syn cyclobutane di-thymine lesions. Here we show that human pol eta can catalyze translesion synthesis past an abasic (AP) site analog, N-2-acetylaminofluorene (AAF)-modified guanine, and a cisplatin-induced intrastrand cross-link between two guanines, Pol eta preferentially incorporated dAMP and dGMP opposite AP, and dCMP opposite AAF-G and cisplatin-GG, but other nucleotides were also incorporated opposite these lesions. However, after incorporating an incorrect nucleotide opposite a lesion, pol eta could not continue chain elongation. In contrast, after incorporating the correct nucleotide opposite a lesion, pol eta could continue chain elongation, whereas pol alpha could not. Thus, the fidelity of translesion synthesis by human pol eta relies not only on the ability of this enzyme to incorporate the correct nucleotide opposite a lesion, but also on its ability to elongate only DNA chains that have a correctly incorporated nucleotide opposite a lesion.
引用
收藏
页码:3100 / 3109
页数:10
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