The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression.
The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression.
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发表时间：
2000-02
期刊：
影响因子：
11.2
通讯作者：
W. Edelmann;A. Umar;Kang Yang;J. Heyer;M. Kucherlapati;M. Lia;B. Kneitz;E. Avdievich;K. Fan;Edmund Wong;G. Crouse;T. Kunkel;M. Lipkin;R. Kolodner;R. Kucherlapati
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作者：
W. Edelmann;A. Umar;Kang Yang;J. Heyer;M. Kucherlapati;M. Lia;B. Kneitz;E. Avdievich;K. Fan;Edmund Wong;G. Crouse;T. Kunkel;M. Lipkin;R. Kolodner;R. Kucherlapati
哺乳动物细胞中DNA错配的修复是由两个高度保守的基因家族成员的蛋白质复合物介导的，即MutS和MutL同源物。MSH2、MSH6、MLH1和PMS2这几个家族成员的种系突变是遗传性非息肉病性结直肠癌的原因，但不是MSH3。为了检验MSH3的作用，我们制造了一只该基因无突变的小鼠。来自Msh3-/-小鼠的细胞在插入/删除错配修复方面存在缺陷，但可以修复碱基错配。Msh3-/-小鼠发生肿瘤的年龄较晚。当Msh3-/-和Msh6-/-突变组合时，肿瘤易感性表型与Msh2-/-或Mlh1-/-小鼠无法区分。这些结果提示MSH3与MSH6协同抑制肿瘤。
Repair of mismatches in DNA in mammalian cells is mediated by a complex of proteins that are members of two highly conserved families of genes referred to as MutS and MutL homologues. Germline mutations in several members of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis colorectal cancer. To examine the role of MSH3, we generated a mouse with a null mutation in this gene. Cells from Msh3-/- mice are defective in repair of insertion/ deletion mismatches but can repair base-base mismatches. Msh3-/- mice develop tumors at a late age. When the Msh3-/- and Msh6-/- mutations are combined, the tumor predisposition phenotype is indistinguishable from Msh2-/- or Mlh1-/- mice. These results suggest that MSH3 cooperates with MSH6 in tumor suppression.