Hsieh Peggy, Yamane Kazuhiko
Genetics & Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Mech Ageing Dev. 2008 Jul-Aug;129(7-8):391-407. doi: 10.1016/j.mad.2008.02.012. Epub 2008 Mar 4.
DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.
DNA错配修复（MMR）蛋白在一系列重要的细胞功能中普遍发挥作用。在其参与复制后修复的过程中，MMR通过纠正复制错误产生的碱基错配来保护基因组。从细菌到人类，MMR功能的丧失会导致生物体中自发突变率大幅增加。MMR基因的突变会引发遗传性非息肉病性结直肠癌，而MMR功能的丧失与相当一部分散发性癌症相关。鉴于其在避免突变方面的突出作用以及靶向一系列DNA损伤的能力，MMR一直是衰老机制研究的对象。本综述总结了关于MMR途径的分子细节以及MMR蛋白在癌症易感性和衰老中的作用的已知信息。
