Unlocking the sugar "steric gate" of DNA polymerases.

Unlocking the sugar "steric gate" of DNA polymerases.
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解锁 DNA 聚合酶的糖“空间门”。

DOI:
10.1021/bi101915z
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发表时间:
2011-02-22
期刊:
影响因子:
2.9
通讯作者:
Suo Z
Suo Z
中科院分区:
生物学3区
文献类型:
--
作者:
Brown JA;Suo Z

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为了保持基因组的稳定性,DNA合成过程中的核糖核苷酸掺入主要在DNA聚合酶水平上进行控制。进入的核糖核苷酸的2′-羟基和大的活性位点残基之间的空间冲突,称为“空间门”,为大多数DNA聚合酶建立了选择性插入脱氧核糖核苷酸的有效机制。最近的动力学,结构,和在体内的研究已经阐明了新的功能有关的核糖核苷酸排斥和核糖核苷酸错误掺入的下游事件的机械后果,如旁路的核糖核苷酸在DNA模板和随后的延伸的DNA损伤旁路产品。这些重要的发现总结在这篇评论文章。
To maintain genomic stability, ribonucleotide incorporation during DNA synthesis is controlled predominantly at the DNA polymerase level. A steric clash between the 2′-hydroxyl of an incoming ribonucleotide and a bulky active site residue, known as the ‘steric gate’, establishes an effective mechanism for most DNA polymerases to selectively insert deoxyribonucleotides. Recent kinetic, structural, and in vivo studies have illuminated novel features about ribonucleotide exclusion and the mechanistic consequences of ribonucleotide misincorporation on downstream events, such as the bypass of a ribonucleotide in a DNA template and the subsequent extension of the DNA lesion bypass product. These important findings are summarized in this review article.
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