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DNA错配修复与基因不稳定

DNA mismatch repair and genetic instability.

作者信息

Harfe B D, Jinks-Robertson S

机构信息

Department of Biology, Emory University, Atlanta, Georgia 30322, USA.

出版信息

Annu Rev Genet. 2000;34:359-399. doi: 10.1146/annurev.genet.34.1.359.

DOI:10.1146/annurev.genet.34.1.359
PMID:11092832
Abstract

Mismatch repair (MMR) systems play a central role in promoting genetic stability by repairing DNA replication errors, inhibiting recombination between non-identical DNA sequences and participating in responses to DNA damage. The discovery of a link between human cancer and MMR defects has led to an explosion of research on eukaryotic MMR. The key proteins in MMR are highly conserved from bacteria to mammals, and this conservation has been critical for defining the components of eukaryotic MMR systems. In eukaryotes, there are multiple homologs of the key bacterial MutS and MutL MMR proteins, and these homologs form heterodimers that have discrete roles in MMR-related processes. This review describes the genetic and biochemical approaches used to study MMR, and summarizes the diverse roles that MMR proteins play in maintaining genetic stability.

摘要

错配修复(MMR)系统通过修复DNA复制错误、抑制非同源DNA序列之间的重组以及参与对DNA损伤的反应,在促进遗传稳定性方面发挥着核心作用。人类癌症与MMR缺陷之间联系的发现引发了对真核生物MMR的大量研究。MMR中的关键蛋白从细菌到哺乳动物高度保守,这种保守性对于确定真核生物MMR系统的组成部分至关重要。在真核生物中,关键的细菌MutS和MutL MMR蛋白有多个同源物,这些同源物形成异源二聚体,在与MMR相关的过程中发挥着不同的作用。本综述描述了用于研究MMR的遗传和生化方法,并总结了MMR蛋白在维持遗传稳定性中所起的多种作用。

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