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. 2025 Jul 9;230(3):iyaf099.
doi: 10.1093/genetics/iyaf099.

MutSgamma promotes meiotic recombination and homolog pairing in mouse spermatocytes

Melissa Frasca  1   2 , Lakshmi Paniker  1 , Rhea Kang  1 , Parijat Chakraborty  1 , Aastha Pandey  1 , Jessica LoPresti  1 , Francesca Cole  1   2
Affiliations

MutSgamma promotes meiotic recombination and homolog pairing in mouse spermatocytes

Melissa Frasca et al. Genetics. .

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.

Keywords: DNA repair; MSH5; MutSgamma; WormBase; homologous recombination; meiosis; mouse; spermatocyte.

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Conflict of interest statement

Conflicts of interest: The author(s) declare no conflicts of interest.

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