THE HUMAN MUTATOR GENE HOMOLOG MSH2 AND ITS ASSOCIATION WITH HEREDITARY NONPOLYPOSIS COLON-CANCER
THE HUMAN MUTATOR GENE HOMOLOG MSH2 AND ITS ASSOCIATION WITH HEREDITARY NONPOLYPOSIS COLON-CANCER
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DOI：
10.1016/0092-8674(93)90546-3
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发表时间：
1993-12-03
期刊：
影响因子：
64.5
通讯作者：
KOLODNER, R
中科院分区：
文献类型：
--
作者：
FISHEL, R;LESCOE, MK;KOLODNER, R
我们已经确定了细菌型和酿酒酵母MSH蛋白的人类同源物，称为HMSH2。 HMSH2在大肠杆菌中的表达会导致显性突变器表型，这表明HMSH2与其他发散的MUTS同源物一样，会干扰正常的细菌不匹配修复途径。 HMSH2向人类染色体2P22-21映射，附近涉及遗传性非跨性病结肠癌（HNPCC）的基因座。在偶发的结肠肿瘤中的剪接受体位点的-6位置和两个小型HNPCC亲属的受影响的个体中，已经检测到T到C转变突变。这些数据和报告表明，酿酒酵母MSH2突变会引起二核苷酸重复的不稳定性，例如与HNPCC相关的重复序列，这表明HMSH2是HNPCC基因。
We have identified a human homolog of the bacterial MutS and S. cerevisiae MSH proteins, called hMSH2. Expression of hMSH2 in E. coli causes a dominant mutator phenotype, suggesting that hMSH2, like other divergent MutS homologs, interferes with the normal bacterial mismatch repair pathway. hMSH2 maps to human chromosome 2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC). A T to C transition mutation has been detected in the -6 position of a splice acceptor site in sporadic colon tumors and in affected individuals of two small HNPCC kindreds. These data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene.