History of DNA polymerase β X-ray crystallography.
History of DNA polymerase β X-ray crystallography.
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DOI：
10.1016/j.dnarep.2020.102928
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发表时间：
2020-09
期刊：
影响因子：
3.8
通讯作者：
Freudenthal BD
中科院分区：
文献类型：
--
作者：
Whitaker AM;Freudenthal BD
DNA聚合酶β（Pol β）是一种在碱基切除修复（BER）途径中参与DNA损伤修复的哺乳动物必需酶。在BER过程中，为了忠实地恢复受损DNA的编码潜能，Pol β首先利用一种裂解酶活性从有切口的BER中间体上移除5′ - 脱氧核糖磷酸部分，随后利用一种DNA合成活性将一个三磷酸核苷酸插入到由此产生的有1个核苷酸缺口的DNA底物中。Pol β的这种DNA合成活性已成为一种模型，用于表征哺乳动物DNA聚合酶在DNA合成过程中所使用的核苷酸转移酶机制的分子步骤。这在一定程度上是因为Pol β极其适合X射线晶体学研究，1994年塞缪尔·威尔逊（Samuel Wilson）博士及其同事发表了无辅基酶大鼠Pol β的首个晶体结构。自这第一个结构以来，威尔逊实验室及其同事已经发表了多达267个Pol β的结构，这些结构代表了不同的配体结合状态、构象、变体和反应中间体。虽然许多实验室对我们理解Pol β做出了重大贡献，但本文的重点是威尔逊实验室长期以来所做出的贡献。我们选择突出一些具有开创性的Pol β结构，并强调每个结构对该领域所做出的总体贡献。
DNA polymerase β (Pol β) is an essential mammalian enzyme involved in the repair of DNA damage during the base excision repair (BER) pathway. In hopes of faithfully restoring the coding potential to damaged DNA during BER, Pol β first uses a lyase activity to remove the 5′-deoxyribose phosphate moiety from a nicked BER intermediate, followed by a DNA synthesis activity to insert a nucleotide triphosphate into the resultant 1-nucleotide gapped DNA substrate. This DNA synthesis activity of Pol β has served as a model to characterize the molecular steps of the nucleotidyl transferase mechanism used by mammalian DNA polymerases during DNA synthesis. This is in part because Pol β has been extremely amenable to X-ray crystallography, with the first crystal structure of apoenzyme rat Pol β published in 1994 by Dr. Samuel Wilson and colleagues. Since this first structure, the Wilson lab and colleagues have published an astounding 267 structures of Pol β that represent different liganded states, conformations, variants, and reaction intermediates. While many labs have made significant contributions to our understanding of Pol β, the focus of this article is on the long history of the contributions from the Wilson lab. We have chosen to highlight select seminal Pol β structures with emphasis on the overarching contributions each structure has made to the field.
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影响因子：
5.7
作者：
Batra, Vinod K.;Beard, William A.;Pedersen, Lars C.;Wilson, Samuel H.
通讯作者：
Wilson, Samuel H.
发现聚合酶诱导的氧化核苷酸的细胞毒性。
影响因子：
64.8
作者：
Freudenthal, Bret D.;Beard, William A.;Perera, Lalith;Shock, David D.;Kim, Taejin;Schlick, Tamar;Wilson, Samuel H.
通讯作者：
Wilson, Samuel H.
影响因子：
2.9
作者：
FREY, MW;SOWERS, LC;BENKOVIC, SJ
通讯作者：
BENKOVIC, SJ
影响因子：
5.7
作者：
Batra, VK;Beard, WA;Wilson, SH
通讯作者：
Wilson, SH
DOI：
10.1073/pnas.1112235108
发表时间：
2012-01-03
影响因子：
11.1
作者：
Batra, Vinod K.;Shock, David D.;Wilson, Samuel H.
通讯作者：
Wilson, Samuel H.