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Updated: Apr 1, 2026

Frequency and Distribution of Crossovers in Caenorhabditis elegans Meiosis by SNP Genotyping using Real-time PCR
Published on: July 11, 2025
Mms4 chromosomal association reveals functional relationships between meiotic crossover pathways in budding yeast
Amamah Farzlin Farnaz1, Sameer Joshi1, Praseetha Sarath1
1School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Trivandrum, India.
Abstract:
Meiotic crossovers are generated from the repair of programmed DNA double-strand breaks (DSBs). In the budding yeast Saccharomyces cerevisiae and mammals, most crossovers are generated through the Class I pathway, involving the mismatch-repair related complex Msh4-Msh5, while a smaller fraction is produced by the Mms4-Mus81 endonuclease (Class II pathway). We present the first report on the genome-wide localization of the Mms4 protein during meiosis in S. cerevisiae. Surprisingly, Mms4 localization showed a trend towards weak DSB sites, unlike the localization of the Class I crossover protein -Msh5, which is biased towards strong DSB sites. This preference for weaker DSB hotspots was retained in a msh5∆ mutant, arguing against competitive models of Mms4 and Msh5 association on meiotic chromosomes. The chromosomal association of Mms4 does not require the formation of meiotic DNA breaks but is facilitated by chromosome axis assembly. These results suggest Mms4 is primarily associated with chromosomal axis regions positioned near recombination intermediates. Mms4 binding is also largely insensitive to heterozygosity, unlike Msh5, consistent with its independence from recombination for localization. Together, these findings support a model in which Mms4-Mus81 enhances the robustness of meiotic recombination with a trend towards binding DSB hotspots that are weaker or are located in regions with sequence divergence that may be processed less efficiently by the Class I pathway.
Insights
Meiotic crossovers form from DNA breaks. The Mms4-Mus81 complex preferentially binds weaker DNA break sites, unlike Msh4-Msh5, enhancing meiotic recombination robustness.
Area of Science:
- * Genetics and Molecular Biology
- * Cell Biology
- * DNA Repair Mechanisms
Background:
- * Meiotic crossovers are essential for accurate chromosome segregation during gamete formation.
- * Crossovers arise from the repair of programmed DNA double-strand breaks (DSBs).
- * Two main pathways exist: Class I (Msh4-Msh5 dependent) and Class II (Mms4-Mus81 endonuclease).
Purpose of the Study:
- * To investigate the genome-wide localization of the Mms4 protein during meiosis in Saccharomyces cerevisiae.
- * To understand the relationship between Mms4 localization and DNA double-strand break sites.
- * To elucidate the role of Mms4 in the context of other meiotic recombination proteins like Msh5.
Main Methods:
- * Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq) to map Mms4 localization.
- * Analysis of Mms4 binding patterns relative to DSB hotspots.
- * Examination of Mms4 localization in various genetic backgrounds, including msh5 deletion mutants.
Main Results:
- * Mms4 exhibits a preference for weaker DSB sites, contrasting with Msh5's bias towards strong DSB sites.
- * Mms4 localization is independent of DSB formation but facilitated by chromosome axis assembly.
- * Mms4 binding is largely insensitive to heterozygosity, unlike Msh5.
Conclusions:
- * Mms4-Mus81 enhances meiotic recombination robustness by targeting weaker or divergent DSB hotspots.
- * Mms4 associates with chromosomal axes near recombination intermediates.
- * Findings challenge competitive models for Mms4 and Msh5 association on meiotic chromosomes.
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