Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853-2703, USA.
Cells. 2021 Apr 20;10(4):948. doi: 10.3390/cells10040948.
The MutL family of DNA mismatch repair proteins (MMR) acts to maintain genomic integrity in somatic and meiotic cells. In baker's yeast, the MutL homolog (MLH) MMR proteins form three heterodimeric complexes, MLH1-PMS1, MLH1-MLH2, and MLH1-MLH3. The recent discovery of human PMS2 (homolog of baker's yeast PMS1) and MLH3 acting independently of human MLH1 in the repair of somatic double-strand breaks questions the assumption that MLH1 is an obligate subunit for MLH function. Here we provide a summary of the canonical roles for MLH factors in DNA genomic maintenance and in meiotic crossover. We then present the phenotypes of cells lacking specific MLH subunits, particularly in meiotic recombination, and based on this analysis, propose a model for an independent early role for MLH3 in meiosis to promote the accurate segregation of homologous chromosomes in the meiosis I division.
MutL 家族的 DNA 错配修复蛋白 (MMR) 作用于维持有丝分裂和减数分裂细胞的基因组完整性。在酿酒酵母中，MutL 同源物 (MLH) MMR 蛋白形成三种异二聚体复合物，MLH1-PMS1、MLH1-MLH2 和 MLH1-MLH3。最近发现人类 PMS2（酵母 PMS1 的同源物）和 MLH3 在修复体细胞双链断裂时独立于人类 MLH1 发挥作用，这对 MLH1 是 MLH 功能必需亚基的假设提出了质疑。在这里，我们总结了 MLH 因子在 DNA 基因组维持和减数分裂交叉中的典型作用。然后，我们介绍了缺乏特定 MLH 亚基的细胞表型，特别是在减数分裂重组中，并基于此分析，提出了 MLH3 在减数分裂中具有独立的早期作用的模型，以促进同源染色体在减数分裂 I 分裂中的准确分离。
