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Updated: Sep 20, 2025
Preparation of Meiotic Chromosome Spreads from Mouse Oocytes for Assessment of Synapsis and Recombination
Published on: July 18, 2025
MutSgamma promotes meiotic recombination and homolog pairing in mouse spermatocytes
Melissa Frasca1,2, Lakshmi Paniker1, Rhea Kang1
1Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Abstract:
DNA repair by homologous recombination is required for parental chromosomes (homologs) to accurately segregate during mammalian meiosis. Meiotic recombination promotes but also relies upon pairing between homologs. This mutual dependence and the differential reliance between recombination and pairing in well-studied organisms have been difficult to deconstruct in the mammalian context. In budding yeast, MutSgamma, a heterodimer between MSH4 and MSH5 promotes crossover-specific recombination by protecting precursors, and in many organisms plays roles in pairing and synaptonemal complex formation. We use recombination and cytological assays to infer the role of MutSgamma in mouse spermatocytes. We find in 2 alleles of Msh5-a null and one bearing a mutation in its ATPase domain, that spermatocytes are severely compromised for recombination producing only a small fraction of noncrossovers. However, they are more proficient in interhomolog pairing particularly on the longer chromosomes than spermatocytes lacking meiotic recombination entirely. We propose that MutSgamma plays an earlier role in mouse than in budding yeast to stabilize D-loops upstream of all interhomolog recombination. Further, that nascent recombination interactions can promote successful interhomolog pairing despite not completing recombination.
Insights
Mouse MutSgamma (MSH4-MSH5) is crucial for DNA repair during meiosis, promoting chromosome pairing and recombination. Its absence impairs recombination but surprisingly enhances chromosome pairing, suggesting an earlier role in stabilizing DNA structures.
Area of Science:
- Genetics
- Cell Biology
- Molecular Biology
Background:
- Homologous recombination is essential for accurate chromosome segregation during mammalian meiosis.
- Meiotic recombination and homolog pairing are interdependent processes, with complex dynamics in mammals.
- MutSgamma (MSH4-MSH5) is known to promote crossover recombination and influence pairing in model organisms like budding yeast.
Purpose of the Study:
- To investigate the role of MutSgamma in mammalian meiosis, specifically in mouse spermatocytes.
- To understand how MutSgamma affects both meiotic recombination and homolog pairing.
- To elucidate the timing and mechanism of MutSgamma function in the mammalian meiotic process.
Main Methods:
- Utilized recombination assays and cytological analysis in mouse spermatocytes.
- Examined the effects of Msh5 null and ATPase-mutant alleles on meiotic progression.
- Compared pairing proficiency in MutSgamma-deficient spermatocytes with those lacking meiotic recombination.
Main Results:
- Spermatocytes with Msh5 mutations showed severely compromised recombination, producing mainly noncrossovers.
- These Msh5-mutant spermatocytes exhibited enhanced interhomolog pairing, especially on longer chromosomes, compared to meiosis-defective controls.
- The findings suggest MutSgamma's role precedes complete recombination initiation in mice.
Conclusions:
- MutSgamma plays an earlier role in mouse meiosis than in budding yeast, potentially stabilizing D-loops.
- Nascent recombination interactions, even if incomplete, can facilitate successful interhomolog pairing.
- This study refines our understanding of the interplay between recombination and pairing in mammalian meiosis.
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