Molecular events during translocation and proofreading extracted from 200 static structures of DNA polymerase.

Molecular events during translocation and proofreading extracted from 200 static structures of DNA polymerase.
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DOI:
10.1093/nar/gkw555
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发表时间:
2016-09-06
影响因子:
14.9
通讯作者:
Ren Z
Ren Z
中科院分区:
生物学2区
文献类型:
--
作者:
Ren Z

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B 家族中的 DNA 聚合酶是 DNA 复制的主力,能够高速、高精度地完成大部分工作。该家族中的聚合酶依赖于内置核酸外切酶进行校对。尚未在原子分辨率上观察到在正确的核苷酸掺入后,聚合酶如何在 DNA 模板链上推进一个核苷酸空间,即称为易位的过程。更令人费解的是,引物链被核酸外切酶切除并在发生错误后返回到聚合酶活性位点后,如何避免易位。蛋白质数据库中的数百个结构不知不觉地捕获了易位和校对分叉路径上的结构事件。这项研究分析了 B 族代表性成员的所有可用结构,并揭示了易位和校对过程中精心策划的事件序列。
DNA polymerases in family B are workhorses of DNA replication that carry out the bulk of the job at a high speed with high accuracy. A polymerase in this family relies on a built-in exonuclease for proofreading. It has not been observed at the atomic resolution how the polymerase advances one nucleotide space on the DNA template strand after a correct nucleotide is incorporated, that is, a process known as translocation. It is even more puzzling how translocation is avoided after the primer strand is excised by the exonuclease and returned back to the polymerase active site once an error occurs. The structural events along the bifurcate pathways of translocation and proofreading have been unwittingly captured by hundreds of structures in Protein Data Bank. This study analyzes all available structures of a representative member in family B and reveals the orchestrated event sequence during translocation and proofreading.
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