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Updated: Jun 18, 2026

Preparation of Meiotic Chromosome Spreads from Mouse Oocytes for Assessment of Synapsis and Recombination
Published on: July 18, 2025
Regulation of meiotic recombination via Mek1-mediated Rad54 phosphorylation
Hengyao Niu1, Lihong Wan, Valeria Busygina
1Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
Abstract:
A preference for homologs over sister chromatids in homologous recombination is a fundamental difference in meiotic versus mitotic cells. In budding yeast, the bias for interhomolog recombination in meiosis requires the Dmc1 recombinase and the meiosis-specific kinase Mek1, which suppresses engagement of sister chromatids by the mitotic recombinase Rad51. Here, a combination of proteomic, biochemical, and genetic approaches has identified an additional role for Mek1 in inhibiting the activity of the Rad51 recombinase through phosphorylation of its binding partner, Rad54. Rad54 phosphorylation of threonine 132 attenuates complex formation with Rad51, and a negative charge at this position reduces Rad51 function in vitro and in vivo. Thus, Mek1 phosphorylation provides a dynamic means of controlling recombination partner choice in meiosis in two ways: (1) it reduces Rad51 activity through inhibition of Rad51/Rad54 complex formation, and (2) it suppresses Rad51-mediated strand invasion of sister chromatids via a Rad54-independent mechanism.
Insights
Meiosis uses Mek1 kinase to control DNA recombination by inhibiting Rad51 recombinase activity. This ensures homologs are preferred over sister chromatids, preventing errors during cell division.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Homologous recombination (HR) differs between meiosis and mitosis.
- Meiosis favors interhomolog recombination, while mitosis favors sister chromatid engagement.
- In budding yeast, Dmc1 and Mek1 are crucial for meiotic interhomolog bias, with Mek1 suppressing Rad51 on sister chromatids.
Purpose of the Study:
- To investigate the additional roles of Mek1 in controlling recombination partner choice during meiosis.
- To elucidate the mechanism by which Mek1 regulates the activity of the Rad51 recombinase.
Main Methods:
- Proteomic analysis
- Biochemical assays
- Genetic approaches
Main Results:
- Mek1 inhibits Rad51 activity by phosphorylating its partner, Rad54, at threonine 132.
- Phosphorylation at threonine 132 attenuates Rad51/Rad54 complex formation.
- This phosphorylation reduces Rad51 function both in vitro and in vivo.
- Mek1 also suppresses sister chromatid invasion independently of Rad54.
Conclusions:
- Mek1 phosphorylation of Rad54 is a key mechanism controlling recombination partner choice in meiosis.
- This regulation ensures accurate chromosome segregation by favoring homologs over sister chromatids.
- Mek1 employs dual mechanisms, involving Rad54 and a Rad54-independent pathway, to control Rad51 activity.
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