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Updated: Dec 22, 2025
Preparation of Meiotic Chromosome Spreads from Mouse Oocytes for Assessment of Synapsis and Recombination
Published on: July 18, 2025
Mechanistic Insight into Crossing over during Mouse Meiosis
Shaun E Peterson1, Scott Keeney2, Maria Jasin1
1Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Crossover recombination is critical for meiotic chromosome segregation, but how mammalian crossing over is accomplished is poorly understood. Here, we illuminate how strands exchange during meiotic recombination in male mice by analyzing patterns of heteroduplex DNA in recombinant molecules preserved by the mismatch correction deficiency of Msh2-/- mutants. Surprisingly, MSH2-dependent recombination suppression was not evident. However, a substantial fraction of crossover products retained heteroduplex DNA, and some provided evidence of MSH2-independent correction. Biased crossover resolution was observed, consistent with asymmetry between DNA ends in earlier intermediates. Many crossover products yielded no heteroduplex DNA, suggesting dismantling by D-loop migration. Unlike the complexity of crossovers in yeast, these simple modifications of the original double-strand break repair model-asymmetry in recombination intermediates and D-loop migration-may be sufficient to explain most meiotic crossing over in mice while also addressing long-standing questions related to Holliday junction resolution.
Insights
Meiotic recombination in male mice involves strand exchange and heteroduplex DNA. Simple modifications to DNA repair models, like asymmetry and D-loop migration, explain most crossover events.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Meiotic recombination is essential for accurate chromosome segregation during meiosis.
- The precise mechanisms of mammalian crossover formation remain incompletely understood.
Purpose of the Study:
- To elucidate the process of strand exchange during male mouse meiotic recombination.
- To investigate the role of mismatch repair in shaping crossover outcomes.
Main Methods:
- Analysis of heteroduplex DNA patterns in recombinant molecules from Msh2-deficient mice.
- Examination of crossover products to identify evidence of DNA repair and resolution intermediates.
Main Results:
- MSH2-dependent suppression of recombination was not observed.
- A significant portion of crossover products retained heteroduplex DNA, with some showing MSH2-independent correction.
- Asymmetry in recombination intermediates and D-loop migration were identified as key factors influencing crossover resolution.
Conclusions:
- Meiotic crossing over in mice can be explained by modifications to the double-strand break repair model, including intermediate asymmetry and D-loop migration.
- These mechanisms address fundamental questions about Holliday junction resolution in mammalian meiosis.
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