Centro de Estudios Fotosintéticos y Bioquímicos, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
Mutat Res. 2009 Sep-Dec;682(2-3):110-28. doi: 10.1016/j.mrrev.2009.07.001. Epub 2009 Jul 19.
Mismatch repair (MMR) system maintains genome integrity by correcting mispaired or unpaired bases which have escaped the proofreading activity of DNA polymerases. The basic features of the pathway have been highly conserved throughout evolution, although the nature and number of the proteins involved in the mechanism vary from prokaryotes to eukaryotes and even between humans and plants. Cells deficient in MMR genes have been observed to display a mutator phenotype characterized by an increased rate in spontaneous mutation, instability of microsatellite sequences and illegitimate recombination between diverged DNA sequences. Studies of the mutator phenotype have demonstrated a critical role for the MMR system in mutation avoidance and genetic stability. Here, we briefly review our current knowledge of the MMR mechanism and then focus on the in vivo biochemical and genetic assays used to investigate the function of the MMR proteins in processing DNA mismatches generated during replication and mitotic recombination in Escherichia coli, Saccharomyces cerevisiae, Homo sapiens and Arabidopsis thaliana. An overview of the biochemical assays developed to study mismatch correction in vitro is also provided.
错配修复（MMR）系统通过纠正已逃脱 DNA 聚合酶校对活性的错配或未配对碱基来维持基因组完整性。尽管参与该机制的蛋白质的性质和数量在从原核生物到真核生物甚至在人类和植物之间有所不同，但该途径的基本特征在进化过程中得到了高度保守。已经观察到缺乏 MMR 基因的细胞表现出突变体表型，其特征是自发突变率增加、微卫星序列不稳定以及分化 DNA 序列之间的不合法重组。对突变体表型的研究表明，MMR 系统在避免突变和遗传稳定性方面起着关键作用。在这里，我们简要回顾了我们对 MMR 机制的当前认识，然后重点介绍了用于研究 MMR 蛋白在复制和有丝分裂重组过程中处理大肠杆菌、酿酒酵母、人类和拟南芥中产生的 DNA 错配的体内生化和遗传测定。还提供了用于研究体外错配校正的生化测定的概述。
