Research Projects

Meiotic crossovers, initiated from Double Strand Breaks (DSBs), generate genetic diversity and facilitate the accurate segregation of homologous chromosomes during Meiosis I. Mis-segregation during meiosis leads to aneuploid gametes, which can cause congenital birth defects like Down syndrome in humans. The Msh4-Msh5 complex, an evolutionarily conserved mismatch repair protein, promotes crossovers by stabilizing joint molecules like Holliday junctions. However, it is unclear how Msh4-Msh5 stabilizes Holliday junctions, including binding to both homologous arms, the extent of binding, and the ability to bind both inter-sister and interhomolog Holliday junctions. This information is crucial for testing predictions from current recombination models, such as the presence of intersister and interhomolog recombination hotspots, branch migration, and heteroduplex generation. To facilitate this analysis, a heterozygous yeast model, S288c-sp/YJM789, is proposed. This strain, containing 3 sporulation enhancing QTLs from SK1, undergoes synchronous meiosis similar to SK1. Genome-wide meiotic recombination maps will be generated, followed by ChIP-Seq analysis of Msh5 binding in the hybrid to distinguish between inter-sister and inter-homolog recombination hotspots and determine the extent of heteroduplex formation. This information can provide novel insights into Msh5 binding and test the nature of meiotic recombination intermediates as predicted by current models.