Structural design of a eukaryotic DNA repair polymerase:: DNA polymerase β
Structural design of a eukaryotic DNA repair polymerase:: DNA polymerase β
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DOI：
10.1016/s0921-8777(00)00029-x
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发表时间：
2000-08-30
期刊：
影响因子：
--
通讯作者：
Wilson, SH
中科院分区：
文献类型：
--
作者：
Beard, WA;Wilson, SH
DNA聚合酶是真核生物中最小的DNA聚合酶，用于在DNA修复过程中在短的DNA间隙中合成DNA。它由两个特殊的结构域组成，这些结构域为碱基切除修复（BER）提供必需的酶活性。它的氨基末端结构域具有裂解酶活性，可以去除在BER过程中产生的5'-脱氧核糖磷酸（dRP）中间体。去除dRP部分通常是BER过程中的速率限制步骤。移除该组失败可能会启动替代BER通路。较大的聚合酶结构域具有核苷酸转移酶活性。该结构域具有模块化组织，其子结构域以模板依赖的方式结合双链DNA，催化金属和正确的核苷三磷酸。DNA聚合酶β的x射线晶体结构，无论是否结合底物，都推断出在配体结合时发生结构域、亚结构域和底物构象变化。许多这些构象变化不同于在其他DNA聚合酶的结构中观察到的。这篇综述将研究DNA聚合酶β的结构方面，促进其在BER中的作用。(C) 2000 Elsevier Science B.V.版权所有
DNA polymerase beta, the smallest eukaryotic DNA polymerase, is designed to synthesize DNA in short DNA gaps during DNA repair. It is composed of two specialized domains that contribute essential enzymatic activities to base excision repair (BER). Its amino-terminal domain possesses a lyase activity necessary to remove the 5'-deoxyribose phosphate (dRP) intermediate generated during BER. Removal of the dRP moiety is often the rate-limiting step during BER. Failure to remove this group may initiate alternate BER pathways. The larger polymerase domain has nucleotidyl transferase activity. This domain has a modular organization with sub-domains that bind duplex DNA, catalytic metals, and the correct nucleoside triphosphate in a template-dependent manner. X-ray crystal structures of DNA polymerase beta, with and without bound substrates, has inferred that domain, sub-domain, and substrate conformational changes occur upon ligand binding. Many of these conformational changes are distinct from those observed in structures of other DNA polymerases. This review will examine the structural aspects of DNA polymerase beta that facilitate its role in BER. (C) 2000 Elsevier Science B.V. All rights reserved.