Datta A, Adjiri A, New L, Crouse G F, Jinks Robertson S
Graduate Program in Biochemistry and Molecular Biology, Emory University, Atlanta, Georgia 30322, USA.
Mol Cell Biol. 1996 Mar;16(3):1085-93. doi: 10.1128/MCB.16.3.1085.
Mismatch repair systems correct replication- and recombination-associated mispaired bases and influence the stability of simple repeats. These systems thus serve multiple roles in maintaining genetic stability in eukaryotes, and human mismatch repair defects have been associated with hereditary predisposition to cancer. In prokaryotes, mismatch repair systems also have been shown to limit recombination between diverged (homologous) sequences. We have developed a unique intron-based assay system to examine the effects of yeast mismatch repair genes (PMS1, MSH2, and MSH3) on crossovers between homologous sequences. We find that the apparent antirecombination effects of mismatch repair proteins in mitosis are related to the degree of substrate divergence. Defects in mismatch repair can elevate homologous recombination between 91% homologous substrates as much as 100-fold while having only modest effects on recombination between 77% homologous substrates. These observations have implications for genome stability and general mechanisms of recombination in eukaryotes.
错配修复系统可纠正与复制和重组相关的错配碱基,并影响简单重复序列的稳定性。因此,这些系统在维持真核生物遗传稳定性方面发挥着多种作用,而人类错配修复缺陷与遗传性癌症易感性有关。在原核生物中,错配修复系统也已被证明可限制分歧(同源)序列之间的重组。我们开发了一种独特的基于内含子的检测系统,以研究酵母错配修复基因(PMS1、MSH2和MSH3)对同源序列之间交叉的影响。我们发现,错配修复蛋白在有丝分裂中的明显抗重组作用与底物分歧程度有关。错配修复缺陷可使91%同源底物之间的同源重组提高多达100倍,而对77%同源底物之间的重组影响较小。这些观察结果对真核生物的基因组稳定性和重组的一般机制具有启示意义。