Selva E M, Maderazo A B, Lahue R S
Department of Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester 01655-0103, USA.
Mol Gen Genet. 1997 Dec;257(1):71-82. doi: 10.1007/pl00008619.
The products of the yeast mismatch repair genes MSH2 and MSH3 participate in the inhibition of genetic recombination between homeologous (divergent) DNA sequences. In strains deficient for these genes, homeologous recombination rates between repeated elements are elevated due to the loss of this inhibition. In this study, the effects of these mutations were further analyzed by quantitation of mitotic homeologous recombinants as crossovers, gene conversions or exceptional events in wild-type, msh2, msh3 and msh2 msh3 mutant strains. When homeologous sequences were present as a direct repeat in one orientation, crossovers and gene conversions were elevated in msh2, msh3 and msh2 msh3 strains. The increases were greater in the msh2 msh3 double mutant than in either single mutant. When the order of the homeologous sequences was reversed, the msh2 mutation again yielded increased rates of crossovers and gene conversions. However, in an msh3 strain, gene conversions occurred at higher levels but interchromosomal crossovers were not increased and intrachromosomal crossovers were reduced relative to wild type. The msh2 msh3 double mutant behaved like the msh2 single mutant in this orientation. Control strains harboring homologous duplications were largely but not entirely unaffected in mutant strains, suggesting specificity for the mismatched intermediates of homeologous recombination. In all strains, very few (< 10%) recombinants could be attributed to exceptional events. These results suggest that MSH2 and MSH3 can function differentially to control homeologous exchanges.
酵母错配修复基因MSH2和MSH3的产物参与抑制同源（不同源）DNA序列之间的基因重组。在这些基因缺陷的菌株中，由于这种抑制作用的丧失，重复元件之间的同源重组率升高。在本研究中，通过对野生型、msh2、msh3和msh2 msh3突变菌株中有丝分裂同源重组体作为交换、基因转换或异常事件进行定量分析，进一步研究了这些突变的影响。当同源序列以一个方向呈同向重复存在时，msh2、msh3和msh2 msh3菌株中的交换和基因转换增加。msh2 msh3双突变体中的增加幅度大于任一单突变体。当同源序列的顺序颠倒时，msh2突变再次导致交换和基因转换率增加。然而，在msh3菌株中，基因转换水平较高，但与野生型相比，染色体间交换没有增加，染色体内交换减少。msh2 msh3双突变体在这个方向上的表现与msh2单突变体相似。携带同源重复的对照菌株在突变菌株中基本但并非完全不受影响，这表明对同源重组错配中间体具有特异性。在所有菌株中，极少数（<10%）重组体可归因于异常事件。这些结果表明，MSH2和MSH3可以发挥不同的功能来控制同源交换。
