Genetic dissection of crossover mutants defines discrete intermediates in mouse meiosis

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 knowl-edge 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.

Automated summary

In yeast, the stabilized 3' end annealed with the homolog is identified as the first detectible CO precursor, while in mice, the CO precursor may include asymmetric SEI-like intermediates and dHJs. Unlike yeast, MLH3 is structurally required to differentiate CO precursors into dHJs in mice. This study provides insights into the mechanism of CO formation and highlights both conservation and unique features of meiotic recombination in mice.