Direct binding of chromosome axis and cohesin complexes underlies meiotic chromosome architecture in fungi and plants

Abstract In prophase of meiosis I, the proteinaceous chromosome axis provides a scaffold for the compaction of chromosomes into a linear loop array, controls the formation of interhomolog crossovers, and finally becomes integrated into the synaptonemal complex after crossovers have formed. Despite its fundamental importance, how the proteins of the meiotic chromosome axis – meiotic HORMADs, axis core proteins, and cohesin complexes – self-assemble with one another is incompletely understood. In particular, it remains unknown how cohesin complexes interact with other axis components. Here, we combine genetics in S. cerevisiae , AlphaFold-based protein interaction screens, and biochemical assays to reveal that a conserved motif in the S. cerevisiae axis core protein Red1 – the cohesin-interacting motif or CIM – binds the C-terminal winged helix domain of cohesin’s meiosis-specific kleisin subunit Rec8. Disrupting the Red1 CIM specifically reduces Rec8-dependent Red1 association with meiotic chromosomes, and results in a strong spore viability defect. Finally, we find that the identified axis core-kleisin interaction is conserved across fungi and plants, but not in mammals, suggesting that different eukaryotic phyla use distinct protein-protein interfaces to assemble the chromosome axis.