Meiotic cohesin paralogs govern cell survival by exhibiting flexibility in partner choice

Erroneous loading of the ring-shaped cohesin complex, especially at centromeres, cause chromosomal segregation defects in both mitosis and meiosis. Mitotic cohesin subunits of this complex, either get replaced or co-exist with their meiotic paralogs during meiosis and also in certain cancers. However, it is unclear whether meiotic paralogs can partner mitotic subunits to form hybrid complexes in somatic cells and if there are any functional consequences on cancer progression. Here, we provide a conceptual framework for the principles of cohesin complex assembly involving non-canonical subunits in proliferating Schizosaccharomyces pombe . We show that chromosome loading, segregation fidelity and cellular proliferation are critically affected by the composition of the available cohesin complexes. We find stark differences in the ability of the meiotic kleisin subunit Rec8 to support robust centromere loading, irrespective of its partner, when compared to the canonical mitotic paralog Rad21. Such variations in cellular growth can be explained by different dwell times of these cohesin complexes on the chromosomes as determined by single-molecule tracking and altered chromatin enrichment. We also discover a unique feature of Rec8, in stabilizing chromatin-bound hypomorphic cohesin mutants that aid in cell survival under restrictive conditions. Overall, we highlight the flexibility of meiotic cohesins in restoring function, albeit at a fitness cost, in the presence of inactivating cohesin mutations. Such imbalances could be exploited by cancers to aid cell survival, but at the expense of increased aneuploidy and genomic instability.