Recent insight into the kinetic mechanisms and conformational dynamics of Y-Family DNA polymerases.
Recent insight into the kinetic mechanisms and conformational dynamics of Y-Family DNA polymerases.
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DOI：
10.1021/bi5000405
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发表时间：
2014-05-06
期刊：
影响因子：
2.9
通讯作者：
Suo Z
中科院分区：
文献类型：
--
作者：
Maxwell BA;Suo Z
DNA聚合酶催化DNA复制和修复的动力学机制一直是研究的热点。最近发现的y家族DNA聚合酶催化绕过受损的DNA碱基，否则会阻碍复制DNA聚合酶和停止复制叉。与其他5个家族的DNA聚合酶不同，y家族DNA聚合酶具有灵活的、溶剂可及的活性位点，能够耐受各种类型的受损模板碱基，并允许有效的病变旁路。然而，它们混杂的活性位点也导致了远低于其他DNA聚合酶的保真度，并产生了有趣的机制特性。此外，y家族DNA聚合酶具有其他一些独特的结构特征，并且在底物结合和催化过程中经历了一系列不同于复制性DNA聚合酶的构象变化。近年来，预稳态动力学方法已被广泛应用于揭示这些迷人的非典型DNA聚合酶的催化特性的丰富信息。在这里，我们回顾了许多关于y家族DNA聚合酶与未受损和受损DNA底物进行DNA聚合的动力学机制的最新发现，以及这些容易出错的酶在催化过程中所采用的构象动力学。
The kinetic mechanisms by which DNA polymerases catalyze DNA replication and repair have long been areas of active research. Recently discovered Y-family DNA polymerases catalyze the bypass of damaged DNA bases that would otherwise block replicative DNA polymerases and stall replication forks. Unlike DNA polymerases from the five other families, the Y-family DNA polymerases have flexible, solvent-accessible active sites that are able to tolerate various types of damaged template bases and allow for efficient lesion bypass. Their promiscuous active sites, however, also lead to fidelities that are much lower than those observed for other DNA polymerases and give rise to interesting mechanistic properties. Additionally, the Y-family DNA polymerases have several other unique structural features and undergo a set of conformational changes during substrate binding and catalysis different from those observed for replicative DNA polymerases. In recent years, pre-steady-state kinetic methods have been extensively employed to reveal a wealth of information about the catalytic properties of these fascinating noncanonical DNA polymerases. Here, we review many of the recent findings on the kinetic mechanisms of DNA polymerization with undamaged and damaged DNA substrates by the Y-family DNA polymerases, and the conformational dynamics employed by these error-prone enzymes during catalysis.
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影响因子：
4.8
作者：
Boudsocq, F;Kokoska, RJ;Woodgate, R
通讯作者：
Woodgate, R
影响因子：
15
作者：
Berezhna, Svitlana Y.;Gill, Joshua P.;Lamichhane, Rajan;Millar, David P.
通讯作者：
Millar, David P.
影响因子：
2.9
作者：
Brown, Jessica A.;Fowler, Jason D.;Suo, Zucai
通讯作者：
Suo, Zucai
影响因子：
2.9
作者：
Arndt, JW;Gong, WM;Chan, MK
通讯作者：
Chan, MK
DOI：
10.1073/pnas.0908640106
发表时间：
2009-12-15
影响因子：
11.1
作者：
Christian, Thomas D.;Romano, Louis J.;Rueda, David
通讯作者：
Rueda, David