ISOLATION OF AN HMSH2-P160 HETERODIMER THAT RESTORES DNA MISMATCH REPAIR TO TUMOR-CELLS
ISOLATION OF AN HMSH2-P160 HETERODIMER THAT RESTORES DNA MISMATCH REPAIR TO TUMOR-CELLS
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DOI：
10.1126/science.7604264
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发表时间：
1995-06-30
期刊：
影响因子：
56.9
通讯作者：
MODRICH, P
中科院分区：
文献类型：
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作者：
DRUMMOND, JT;LI, GM;MODRICH, P
凭借其能够恢复hMSH2缺陷型LoVo结直肠肿瘤细胞的核提取物的错配修复能力，从海拉细胞中分离出了hMSH2与一种160千道尔顿多肽的错配结合异二聚体。这种被命名为hMutSα的异二聚体还能恢复对烷基化耐受的MT1淋巴母细胞和HCT - 15结直肠肿瘤细胞提取物的错配修复，这些细胞在碱基 - 碱基和单核苷酸插入 - 缺失错配修复方面存在选择性缺陷。由于HCT - 15细胞似乎没有hMSH2突变，这种选择性修复缺陷可能是hMutSα的160千道尔顿亚基缺乏的结果，并且相应基因的突变可能导致高突变性和癌症易感性。
A mismatch-binding heterodimer of hMSH2 and a 160-kilodalton polypeptide has been isolated from Hela cells by virtue of its ability to restore mismatch repair to nuclear extracts of hMSH2-deficient LoVo colorectal tumor cells. This heterodimer, designated hMutS alpha; also restores mismatch repair to extracts of alkylation-tolerant MT1 lymphoblastoid cells and HCT-15 colorectal tumor cells, which are selectively defective in the repair of base-base and single-nucleotide insertion-deletion mismatches. Because HCT-15 cells appear to be free of hMSH2 mutations, this selective repair defect is likely a result of a deficiency of the hMutS alpha 160-kilodalton subunit, and mutations in the corresponding gene may confer hypermutability and cancer predisposition.