Mechanisms of accurate translesion synthesis by human DNA polymerase η
Mechanisms of accurate translesion synthesis by human DNA polymerase η
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DOI：
10.1093/emboj/19.12.3100
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发表时间：
2000-06-15
期刊：
影响因子：
11.4
通讯作者：
Hanaoka, F
中科院分区：
文献类型：
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作者：
Masutani, C;Kusumoto, R;Hanaoka, F
XPV （xeroderma pigmentosum variant）基因编码人类DNA聚合酶eta (pol eta)，该基因参与受损DNA的复制，pol eta在顺式同步环丁烷二胸腺嘧啶病变后催化高效准确的翻译合成。本研究表明，人类pol - eta可以通过碱性（AP）位点类似物，n- 2-乙酰氨基芴（AAF）修饰的鸟嘌呤，以及顺铂诱导的两个鸟嘌呤之间的链内交联催化翻译合成，pol - eta优先结合AP对面的dAMP和dGMP，以及AAF- g和顺铂- gg对面的dCMP，但其他核苷酸也在这些损伤的对面结合。然而，在病变的对面加入不正确的核苷酸后，pol - eta不能继续延长链。相反，在病变的对面加入正确的核苷酸后，pol - eta可以继续延长链，而pol - alpha则不能。因此，人类pol - eta转译合成的保真度不仅依赖于该酶结合病灶对面正确核苷酸的能力，还依赖于其仅延长具有正确结合病灶对面核苷酸的DNA链的能力。
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.