The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations
The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations
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DOI：
10.1073/pnas.95.21.12404
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发表时间：
1998-10-13
影响因子：
11.1
通讯作者：
Kolodner, RD
中科院分区：
文献类型：
--
作者：
Flores-Rozas, H;Kolodner, RD
酿酒酵母基因组编码四种MutL同源物，其中，已知MLH 1和PMS 1在修复DNA错配的MSH 2依赖性途径中起作用。我们研究了MLH 3在错配修复中的作用。MLH 3中的突变通过在7个Ts的运行中增加单个T的缺失率来增加hom 3 -10等位基因的回复率。MLH 3和MSH 6中突变的组合引起hom 3 -10回复率的协同增加，而mlh 3 msh 3双突变体中的hom 3 -10回复率与相应的单突变体中相同。当分析LYS 2基因中移码热点处的突变累积时，观察到类似的结果，尽管MLH 3的突变在每个LYS 2移码热点处不引起相同程度的影响。MLH 3与MLH 1在双杂交系统中相互作用。这些数据与这样的想法一致，即通过MSH 3依赖性错配修复途径修复特定插入/缺失错配的一部分使用异二聚体MLH 1-MLH 3复合物代替MLH 1-PMS 1复合物。
The Saccharomyces cerevisiae genome encodes four MutL homologs, Of these, MLH1 and PMS1 are known to act in the MSH2-dependent pathway that repairs DNA mismatches. We have investigated the role of MLH3 in mismatch repair. Mutations in MLH3 increased the rate of reversion of the hom3-10 allele by increasing the rate of deletion of a single T in a run of 7 Ts. Combination of mutations in MLH3 and MSH6 caused a synergistic increase in the hom3-10 reversion rate, whereas the hom3-10 reversion rate in an mlh3 msh3 double mutant was the same as in the respective single mutants. Similar results were observed when the accumulation of mutations at frameshift hot spots in the LYS2 gene was analyzed, although mutation of MLH3 did not cause the same extent of affect at every LYS2 frameshift hot spot. MLH3 interacted with MLH1 in a two-hybrid system. These data are consistent with the idea that a proportion of the repair of specific insertion/deletion mispairs by the MSH3-dependent mismatch repair pathway uses a heterodimeric MLH1-MLH3 complex in place of the MLH1-PMS1 complex.