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DNA 聚合酶为跨损伤合成提供了一套策略,以克服氧化生成的损伤。

DNA polymerases provide a canon of strategies for translesion synthesis past oxidatively generated lesions.

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. 2011 Jun;21(3):358-69. doi: 10.1016/j.sbi.2011.03.008. Epub 2011 Apr 7.

Abstract

Deducing the structure of the DNA double helix in 1953 implied the mode of its replication: Watson-Crick (WC) base pairing might instruct an enzyme, now known as the DNA polymerase, during the synthesis of a daughter stand complementary to a single strand of the parental double helix. What has become increasingly clear in the last 60 years, however, is that adducted and oxidatively generated DNA bases are ubiquitous in physiological DNA, and all organisms conserve multiple DNA polymerases specialized for DNA synthesis opposite these damaged templates. Here, we review recent crystal structures depicting replicative and bypass DNA polymerases encountering two typical lesions arising from the oxidation of DNA: abasic sites, which block the replication fork, and the miscoding premutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoG).

摘要

1953 年,推断 DNA 双螺旋结构意味着其复制模式:沃森-克里克(WC)碱基配对可能指导一种酶,现在称为 DNA 聚合酶,在合成与亲本 DNA 双螺旋中一条单链互补的子链时发挥作用。然而,在过去的 60 年中,越来越明显的是,加合物和氧化生成的 DNA 碱基在生理 DNA 中普遍存在,所有生物体都保留了多种专门用于在这些受损模板上合成 DNA 的 DNA 聚合酶。在这里,我们回顾了最近描述复制和旁路 DNA 聚合酶遇到两种典型 DNA 氧化损伤的晶体结构:碱基缺失,其阻断复制叉;以及易错的前诱变损伤 7,8-二氢-8-氧鸟嘌呤(8-氧鸟嘌呤)。

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