Jiricny J
Institute of Medical Radiobiology of the University of Zürich, Switzerland.
Mutat Res. 1998 Dec 14;409(3):107-21. doi: 10.1016/s0921-8777(98)00056-1.
The discovery that mutations in mismatch repair genes segregate with hereditary nonpolyposis colon cancer has awakened a great deal of interest in the study of the process of postreplicative mismatch repair. The characterisation of the principal players involved in this important metabolic pathway has been greatly facilitated by the amino acid sequence conservation among functional homologues of bacteria, yeast and mammals. The phenotypes of mismatch repair deficient mutants are also similar in many ways. In humans, mismatch repair malfunction demonstrates itself in the form of a mutator phenotype of the affected cells, an instability of microsatellite sequences and increased levels of somatic recombination. Moreover, mismatch repair deficient cells display also varying levels of tolerance to DNA damaging agents and are thought to be involved in the cell killing mediated by these agents. This article discusses some recent developments in this fast-moving field.
错配修复基因中的突变与遗传性非息肉病性结肠癌相关这一发现，引发了人们对复制后错配修复过程研究的浓厚兴趣。细菌、酵母和哺乳动物功能同源物之间的氨基酸序列保守性极大地促进了对这一重要代谢途径中主要参与者的表征。错配修复缺陷突变体的表型在许多方面也相似。在人类中，错配修复功能障碍表现为受影响细胞的突变体表型、微卫星序列的不稳定性以及体细胞重组水平的增加。此外，错配修复缺陷细胞对DNA损伤剂也表现出不同程度的耐受性，并被认为参与了这些试剂介导的细胞杀伤。本文讨论了这个快速发展领域的一些最新进展。
