Corentin Claeys Bouuaert: Deciphering molecular mechanisms involved in the formation and repair of meiotic DNA double-strand breaks in S. cerevisiae.

The programmed induction of DNA double-strand breaks (DSB) during meiosis and their repair by homologous recombination is essential for the accurate segregation of homologous chromosome and promotes genetic diversity, providing a key driving force for evolution in eukaryotes. Meiotic DSB formation and recombination involves elaborate molecular mechanisms that are still incompletely understood. In this talk, I will present two ongoing studies from my lab, aimed at gaining new molecular insights into these biological processes, using budding yeast as a model.

The first story relates to the relationship between meiotic DSB formation and the chromosome axis. During meiosis, chromosomes fold as linear arrays of loops anchored along a proteinaceous axis that controls every aspect of meiotic recombination. In S. cerevisiae, the meiotic chromosome axis includes a HORMA-domain containing protein, Hop1, that plays a key role in promoting DSB formation. Through AlphaFold modeling, biochemical reconstitution, and molecular genetics approaches in yeast, we found that Hop1 recruits the essential DSB factor, Mer2 through a dual interaction mechanism. This mechanism may participate in controlling the genome-wide distribution of meiotic DSBs.

The second story relates to the potential role of biomolecular condensation in the formation of meiotic crossovers. Crossovers form within protein-dense spherical structures called recombination nodules. Recent models suggest that recombination nodules are active droplets containing crossover-promoting factors, assembled by a mechanism of biomolecular condensation. In S. cerevisiae, a central crossover factor is Zip3. We have used a biochemical approach to probe the molecular properties of Zip3 and have characterized the relationships between its structural organization, its protein-protein interactions, and crossover formation. Our findings shed light on the intrinsic properties of Zip3 and may have implications for the mechanism of crossover regulation.