INACTIVATION OF THE MOUSE MSH2 GENE RESULTS IN MISMATCH REPAIR DEFICIENCY, METHYLATION TOLERANCE, HYPERRECOMBINATION, AND PREDISPOSITION TO CANCER
INACTIVATION OF THE MOUSE MSH2 GENE RESULTS IN MISMATCH REPAIR DEFICIENCY, METHYLATION TOLERANCE, HYPERRECOMBINATION, AND PREDISPOSITION TO CANCER
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DOI：
10.1016/0092-8674(95)90319-4
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发表时间：
1995-07-28
期刊：
影响因子：
64.5
通讯作者：
RIELE, HT
中科院分区：
文献类型：
--
作者：
DEWIND, N;DEKKER, M;RIELE, HT
为了研究假定的 DNA 错配修复 (MMR) 基因 Msh2 在基因组稳定性和肿瘤发生中的作用，我们培育了缺乏该基因的细胞和小鼠。 Msh2 缺陷细胞失去了错配结合，并获得了微卫星不稳定性、突变表型和对甲基化剂的耐受性。此外，在这些细胞中，同源重组不再依赖于相互作用的 DNA 序列之间的完全同一性，这表明 Msh2 参与保护基因组免于混杂重组。 Msh2 缺陷小鼠没有表现出重大异常，但很大一部分在幼年时就患上了淋巴瘤。因此，Msh2 参与 MMR，控制基因组稳定性的多个方面；错配修复（MMR）控制的基因组稳定性的丧失易患癌症。
To investigate the role of the presumed DNA mismatch repair (MMR) gene Msh2 in genome stability and tumorigenesis, we have generated cells and mice that are deficient for the gene. Msh2-deficient cells have lost mismatch binding and have acquired microsatellite instability, a mutator phenotype, and tolerance to methylating agents. Moreover, in these cells, homologous recombination has lost dependence on complete identity between interacting DNA sequences, suggesting that Msh2 is involved in safeguarding the genome from promiscuous recombination. Msh2-deficient mice display no major abnormalities, but a significant fraction develops lymphomas at an early age. Thus, Msh2 is involved in MMR, controlling several aspects of genome stability; loss of MMR-controlled genome stability predisposes to cancer.