hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6
hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6
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DOI：
10.1073/pnas.93.24.13629
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发表时间：
1996-11-26
影响因子：
11.1
通讯作者：
Fishel, R
中科院分区：
文献类型：
--
作者：
Acharya, S;Wilson, T;Fishel, R
对人MutS同源基因hMSH 2、hMSH 3和hMSH 6的遗传和生化特性进行了研究。分离并鉴定了hMSH 6的全长cDNA和基因组位点，结果表明hMSH 6基因由10个外显子组成，定位于染色体2 p15 -16，在某些情况下，发现hMSH 3 cDNA含有27-bp缺失，导致9个氨基酸的缺失，这取决于分离cDNA的个体，hMSH 2，hMSH 3，和hMSH 6都显示出相似的组织特异性表达模式，hMSH 2蛋白与hMSH 3和hMSH 6蛋白形成复合物，类似于酿酒酵母MSH 2、MSH 3和MSH 6的研究所证明的蛋白复合物。还发现hMSH 2形成同源多聚体复合物，但hMSH 3和hMSH 6似乎都不与它们自身或彼此相互作用。对hMSH 2-hMSH 3和hMSH 2-hMSN 6蛋白复合物的错配核苷酸结合特异性的分析显示它们具有重叠但不相同的结合特异性，这些结果有助于解释遗传性非息肉病性结肠癌中不同错配修复基因突变的分布。
The genetic and biochemical properties of three human MutS homologues, hMSH2, hMSH3, and hMSH6, have been examined, The full-length hMSH6 cDNA and genomic locus were isolated and characterized, and it was demonstrated that the hMSH6 gene consisted of 10 exons and mapped to chromosome 2p15-16, The hMSH3 cDNA was in some cases found to contain a 27-bp deletion resulting in a loss of nine amino acids, depending on the individual from which the cDNA was isolated, hMSH2, hMSH3, and hMSH6 all showed similar tissue-specific expression patterns, hMSH2 protein formed a complex with both hMSH3 and hMSH6 proteins, similar to protein complexes demonstrated by studies of the Saccharomyces cerevisiae MSH2, MSH3, and MSH6. hMSH2 was also found to form a homomultimer complex, but neither hMSH3 nor hMSH6 appear to interact with themselves or each other, Analysis of the mismatched nucleotide-binding specificity of the hMSH2-hMSH3 and hMSH2-hMSN6 protein complexes showed that they have overlapping but not identical binding specificity, These results help to explain the distribution of mutations in different mismatch-repair genes seen in hereditary nonpolyposis colon cancer.