Functional specificity of MutL homologs in yeast: Evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction
Functional specificity of MutL homologs in yeast: Evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction
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DOI：
10.1073/pnas.96.24.13914
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发表时间：
1999-11-23
影响因子：
11.1
通讯作者：
Hunter, N
中科院分区：
文献类型：
--
作者：
Wang, TF;Kleckner, N;Hunter, N
酵母基因组编码与细菌错配修复组分MutL同源的四种蛋白质（Pms 1和Mlh 1 -3）。使用两种杂交相互作用和免疫共沉淀研究。我们发现这些蛋白质在体内只能形成三种类型的复合物。Mlh 1是所有三种复合物的共同组分，与Pms 1、Mlh 2和Mlh 3相互作用，推测为异二聚体。单缺失突变体的表型揭示了三种异源二聚体在减数分裂期间的不同功能：在pms 1突变体中，频繁的减数分裂后分离表明异源双链DNA的纠正存在缺陷，而交换频率是正常的。相反，在mlh 3突变体中的交换减少到野生型水平的大约70%，但异源双链体的校正是正常的。在mlh 2突变体中，交换是正常的，未观察到减数分裂后分离，但非孟德尔分离升高，并相对于奇偶性改变。最后，大致上，mlh 1突变体代表了组合的单突变体表型。两者合计，这些数据意味着通过与其他三个MutL同源物组合的基本Mlh 1功能的调制，并特别表明MutL与Mlh 3组合，以促进减数分裂交换。
The yeast genome encodes four proteins (Pms1 and Mlh1-3) homologous to the bacterial mismatch repair component, MutL. Using two hybrid-interaction and coimmunoprecipitation studies. we show that these proteins can form only three types of complexes in vivo. Mlh1 is the common component of ail three complexes, interacting with Pms1, Mlh2, and Mlh3, presumptively as heterodimers. The phenotypes of single deletion mutants reveal distinct functions for the three heterodimers during meiosis: in a pms1 mutant frequent postmeiotic segregation indicates a defect in the correction of heteroduplex DNA, whereas the frequency of crossing-over is normal. Conversely, crossing-over in the mlh3 mutant is reduced to approximate to 70% of wild-type levels but correction of heteroduplex is normal. In a mlh2 mutant, crossing-over is normal and postmeiotic segregation is not observed but non-Mendelian segregation is elevated and altered with respect to parity. Finally, to a first approximation, the mlh1 mutant represents the combined single mutant phenotypes. Taken together, these data imply modulation of a basic Mlh1 function via combination with the three other MutL homologs and suggest specifically that MutL combines with Mlh3 to promote meiotic crossing-over.