Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair
Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair
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DOI：
10.1101/gad.10.4.407
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发表时间：
1996-02-15
影响因子：
10.5
通讯作者：
Kolodner, R
中科院分区：
文献类型：
--
作者：
Marsischky, GT;Filosi, N;Kolodner, R
酿酒酵母编码六个基因，MSH 1 -6，其编码与细菌MutS蛋白相关的蛋白质。在这项研究中，MSH 2，MSH 3和MSH 6在错配修复中的作用已经通过测量含有不同组合的MSH 2，MSH 3和MSH 6突变的菌株中的累积突变和突变谱的速率以及通过研究MSH 2蛋白与MSH 3和MSH 6蛋白之间的物理相互作用来检查。结果表明，S.酿酒酵母有两条MSH 2依赖性错配修复途径：一条识别单碱基错配，需要MSH 2和MSH 6，另一条识别插入/缺失错配，需要MSH 2和MSH 6或MSH 2和MSH 3的组合。MSH 3和MSH 6的冗余解释了HNPCC家族中hmsh 2突变的更高患病率，并建议如何分析hmsh 3和hmsh 6突变在癌症易感性中的作用。
Saccharomyces cerevisiae encodes six genes, MSH1-6, which encode proteins related to the bacterial MutS protein. In this study the role of MSH2, MSH3, and MSH6 in mismatch repair has been examined by measuring the rate of accumulating mutations and mutation spectrum in strains containing different combinations of msh2, msh3, and msh6 mutations and by studying the physical interaction between the MSH2 protein and the MSH3 and MSH6 proteins. The results indicate that S. cerevisiae has two pathways of MSH2-dependent mismatch repair: one that recognizes single-base mispairs and requires MSH2 and MSH6, and a second that recognizes insertion/deletion mispairs and requires a combination of either MSH2 and MSH6 or MSH2 and MSH3. The redundancy of MSH3 and MSH6 explains the greater prevalence of hmsh2 mutations in HNPCC families and suggests how the role of hmsh3 and hmsh6 mutations in cancer susceptibility could be analyzed.