Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex
Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex
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DOI：
10.1016/s0960-9822(06)00337-x
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发表时间：
1997-10-01
期刊：
影响因子：
9.2
通讯作者：
Prakash, S
中科院分区：
文献类型：
--
作者：
Habraken, Y;Sung, P;Prakash, S
DNA错配修复在维持基因组稳定性方面具有关键作用。错配修复缺陷导致自发突变率升高和简单重复序列不稳定性增加，而人类错配修复基因突变导致遗传性非息肉病性结直肠癌[1，2]。错配识别是错配修复的第一个关键步骤。在酵母和人类中的遗传和生物化学研究已经表明在错配识别中需要MSH 2-MSH 3和MSH 2-MSH 6异二聚体。这些复合物在一定程度上具有重叠的错配结合特异性[3-10]。MLH 1和PMS 1是错配修复的其他重要组成部分，但它们在此过程中的功能尚不清楚。我们已经将酵母MLH 1-PMS 1异源二聚体纯化至接近同质，并检测其对MSH 2-MSH 3结合DNA错配的影响。MLH 1-PMS 1复合物本身对错配DNA没有亲和力，但它大大增强了MSH 2-MSH 3的错配结合能力。(C)Current Biology Ltd ISSN 0960-9822。
DNA mismatch repair has a key role in maintaining genomic stability. Defects in mismatch repair cause elevated spontaneous mutation rates and increased instability of simple repetitive sequences, while mutations in human mismatch repair genes result in hereditary nonpolyposis colorectal cancers [1,2]. Mismatch recognition represents the first critical step of mismatch repair. Genetic and biochemical studies in yeast and humans have indicated a requirement for MSH2-MSH3 and MSH2-MSH6 heterodimers in mismatch recognition. These complexes have, to some extent, overlapping mismatch binding specificities [3-10]. MLH1 and PMS1 are the other essential components of mismatch repair, but how they function in this process is not known. We have purified the yeast MLH1-PMS1 heterodimer to near homogeneity, and examined its effect on MSH2-MSH3 binding to DNA mismatches. By itself, the MLH1-PMS1 complex shows no affinity for mismatched DNA, but it greatly enhances the mismatch binding ability of MSH2-MSH3. (C) Current Biology Ltd ISSN 0960-9822.