Karran P, Bignami M
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, UK.
Bioessays. 1994 Nov;16(11):833-9. doi: 10.1002/bies.950161110.
DNA mismatch repair is an important pathway of mutation avoidance. It also contributes to the cytotoxic effects of some kinds of DNA damage, and cells defective in mismatch repair are resistant, or tolerant, to the presence of some normally cytotoxic base analogues in their DNA. The absence of a particular mismatch binding function from some mammalian cells confers resistance to the base analogues O6-methylguanine and 6-thioguanine in DNA. Cells also acquire a spontaneous mutator phenotype as a consequence of this defect. Impaired mismatch binding can cause an instability in DNA microsatellite regions that comprise repeated dinucleotides. Microsatellite DNA instability is common in familial and sporadic colon carcinomas as well as in a number of other tumours. Several independent lines of investigation have identified defects in mismatch repair proteins that are causally related to these cancers.
DNA错配修复是避免突变的重要途径。它也有助于某些类型DNA损伤的细胞毒性作用，错配修复缺陷的细胞对其DNA中某些正常具有细胞毒性的碱基类似物具有抗性或耐受性。一些哺乳动物细胞缺乏特定的错配结合功能，使其对DNA中的碱基类似物O6-甲基鸟嘌呤和6-硫鸟嘌呤具有抗性。由于这种缺陷，细胞还会获得自发突变表型。错配结合受损会导致包含重复二核苷酸的DNA微卫星区域不稳定。微卫星DNA不稳定在家族性和散发性结肠癌以及许多其他肿瘤中很常见。几项独立的研究已经确定错配修复蛋白的缺陷与这些癌症有因果关系。
