遗传剖析交叉突变体定义了小鼠减数分裂中的离散中间产物。
Genetic dissection of crossover mutants defines discrete intermediates in mouse meiosis.
机构信息
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Program in Genetics and Epigenetics, Houston, TX, USA.
Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
出版信息
Mol Cell. 2023 Aug 17;83(16):2941-2958.e7. doi: 10.1016/j.molcel.2023.07.022.
Crossovers (COs), the exchange of homolog arms, are required for accurate chromosome segregation during meiosis. Studies in yeast have described the single-end invasion (SEI) intermediate: a stabilized 3' end annealed with the homolog as the first detectible CO precursor. SEIs are thought to differentiate into double Holliday junctions (dHJs) that are resolved by MutLgamma (MLH1/MLH3) into COs. Currently, we lack knowledge of early steps of mammalian CO recombination or how intermediates are differentiated in any organism. Using comprehensive analysis of recombination in thirteen different genetic conditions with varying levels of compromised CO resolution, we infer CO precursors include asymmetric SEI-like intermediates and dHJs in mouse. In contrast to yeast, MLH3 is structurally required to differentiate CO precursors into dHJs. We verify conservation of aspects of meiotic recombination and show unique features in mouse, providing mechanistic insight into CO formation.
交叉（COs），同源臂的交换，是减数分裂过程中准确染色体分离所必需的。酵母的研究描述了单端入侵（SEI）中间体：稳定的 3'端与同源物退火作为第一个可检测到的 CO 前体。SEIs 被认为分化成双 Holliday 连接体（dHJs），MutLgamma（MLH1/MLH3）将其分解为 COs。目前，我们缺乏对哺乳动物 CO 重组早期步骤的了解，也不知道中间产物在任何生物体中是如何分化的。通过对十三种不同遗传条件下的重组进行综合分析，这些条件的 CO 分辨率不同，我们推断 CO 前体包括不对称 SEI 样中间产物和小鼠中的 dHJs。与酵母不同，MLH3 在结构上需要将 CO 前体分化成 dHJs。我们验证了减数分裂重组的某些方面的保守性，并在小鼠中显示出独特的特征，为 CO 形成提供了机制上的见解。
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