Inefficient bypass of an abasic site by DNA polymerase η
Inefficient bypass of an abasic site by DNA polymerase η
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DOI：
10.1074/jbc.m008021200
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发表时间：
2001-03-02
影响因子：
4.8
通讯作者：
Prakash, L
中科院分区：
文献类型：
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作者：
Haracska, L;Washington, MT;Prakash, L
DNA聚合酶eta（Pol eta）有效而准确地绕过顺式胸腺嘧啶-胸腺嘧啶二聚体，人类Pol eta的失活导致癌症易感综合征，即着色性干皮病的变异形式。此外，Pol eta通过在8-氧代鸟嘌呤损伤的对面插入C而有效地绕过该损伤，并且通过插入C或T而绕过O-6-甲基鸟嘌呤损伤。为了进一步评估Poleta耐受的DNA损伤范围，在这里，我们研究了无碱基位点的旁路，一种典型的非指令性损伤。稳态动力学分析表明，酵母和人Pol eta在插入与脱碱基位点相对的核苷酸和从插入的核苷酸延伸方面都非常低效。因此，Pol eta绕过这种病变非常差。这些结果表明，Pol eta需要存在与引入的核苷酸和引物末端相对的模板碱基以催化有效的核苷酸掺入。
DNA polymerase eta (Pol eta) bypasses a cis-syn thymine-thymine dimer efficiently and accurately, and inactivation of Pol eta in humans results in the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Also, Pol eta bypasses the 8-oxoguanine lesion efficiently by predominantly inserting a C opposite this lesion, and it bypasses the O-6-methylguanine lesion by inserting a C or a T. To further assess the range of DNA lesions tolerated by Pol eta, here we examine the bypass of an abasic site, a prototypical noninstructional lesion. Steady state kinetic analyses show that both yeast and human Pol eta are very inefficient in both inserting a nucleotide opposite an abasic site and in extending from the nucleotide inserted. Hence, Pol eta bypasses this lesion extremely poorly. These results suggest that Pol eta requires the presence of template bases opposite both the incoming nucleotide and the primer terminus to catalyze efficient nucleotide incorporation.