道路上的障碍：复制性DNA聚合酶如何识别DNA损伤。

Bumps in the road: how replicative DNA polymerases see DNA damage.

作者信息

Hogg Matthew, Wallace Susan S, Doublié Sylvie

机构信息

Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.

出版信息

Curr Opin Struct Biol. 2005 Feb;15(1):86-93. doi: 10.1016/j.sbi.2005.01.014.

DOI:10.1016/j.sbi.2005.01.014

PMID:15718138

Abstract

Significant advances have been made recently in the study of polymerases. First came the realization that there are many more DNA polymerases than originally thought; indeed, no fewer than 14 template-dependent DNA polymerases are found in mammals. Concurrent structural studies of DNA polymerases bound to DNA and incoming nucleotide have revealed how these remarkable copying machines select the correct deoxynucleoside triphosphate among a sea of nucleotides. A whole new level of insight into DNA replication fidelity has been reached as a result of recently determined crystal structures of DNA lesions in the context of the active sites of repair, replicative and specialized DNA polymerases. These structures illustrate why some lesions can be bypassed readily, whereas others are strong blocks to DNA replication.

摘要

近年来，聚合酶的研究取得了重大进展。首先，人们认识到DNA聚合酶的种类比最初想象的要多得多；事实上，在哺乳动物中发现了不少于14种依赖模板的DNA聚合酶。同时，对与DNA和即将进入的核苷酸结合的DNA聚合酶的结构研究揭示了这些非凡的复制机器如何在众多核苷酸中选择正确的脱氧核苷三磷酸。由于最近确定了修复、复制和特殊DNA聚合酶活性位点背景下DNA损伤的晶体结构，人们对DNA复制保真度有了全新的认识。这些结构说明了为什么有些损伤可以很容易地被绕过，而有些则是DNA复制的强大障碍。