de Wind N, Dekker M, Berns A, Radman M, te Riele H
Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam.
Cell. 1995 Jul 28;82(2):321-30. doi: 10.1016/0092-8674(95)90319-4.
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.
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，我们构建了该基因缺陷的细胞和小鼠。Msh2缺陷的细胞失去了错配结合能力，并获得了微卫星不稳定性、突变体表型以及对甲基化试剂的耐受性。此外，在这些细胞中，同源重组失去了对相互作用DNA序列之间完全一致性的依赖性，这表明Msh2参与保护基因组免受杂乱重组的影响。Msh2缺陷的小鼠没有明显的异常，但有很大一部分在幼年时发生淋巴瘤。因此，Msh2参与错配修复，控制基因组稳定性的多个方面；错配修复控制的基因组稳定性丧失易引发癌症。
