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Structure and Mechanism of DNA Polymerase β

机译:DNA聚合酶β的结构与机理

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摘要

DNA polymerase (pol) β is a small eukaryotic DNA polymerase composed of two domains. Each domain contributes an enzymatic activity (DNA synthesis and deoxyribose phosphate lyase) during the repair of simple base lesions. These domains are termed the polymerase and lyase domains, respectively. Pol β has been an excellent model enzyme for studying the nucleotidyl transferase reaction and substrate discrimination at a molecular level. In this review, recent crystallographic studies of pol β in various liganded and conformational states during the insertion of right and wrong nucleotides as well as during the bypass of damaged DNA (apurinic sites and 8-oxoguanine) are described. Structures of these catalytic intermediates provide unexpected insights into mechanisms by which DNA polymerases enhance genome stability. These structures also provide an improved framework that permits computational studies to facilitate the interpretation of detailed kinetic analyses of this model enzyme.
机译:DNA聚合酶(pol)β是由两个结构域组成的小型真核DNA聚合酶。在修复简单的基础病变过程中,每个结构域均具有酶促活性(DNA合成和脱氧核糖磷酸裂解酶)。这些结构域分别称为聚合酶和裂解酶结构域。 Polβ是一种优秀的模型酶,可用于在分子水平上研究核苷酸转移酶反应和底物识别。在这篇综述中,描述了在插入正确和错误的核苷酸以及绕过受损的DNA(紫杉醇位点和8-氧代鸟嘌呤)过程中,在各种配体和构象状态下的polβ的最新晶体学研究。这些催化中间体的结构为DNA聚合酶增强基因组稳定性的机制提供了意想不到的见解。这些结构还提供了改进的框架,该框架允许进行计算研究以促进对该模型酶的详细动力学分析的解释。

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