Studying meiotic cohesin in somatic cells reveals that Rec8-containing cohesin requires Stag3 to function and is regulated by Wapl and sororin

The DNA embracing, ring-shaped, multiprotein complex cohesin mediates sister chromatid cohesion and is stepwise displaced in mitosis by Wapl and Separase to facilitate anaphase. Proper regulation of chromosome cohesion throughout meiosis is critical to prevent formation of aneuploid gametes, which are associated with trisomies and infertility in humans. Studying cohesion in meiocytes is complicated by their difficult experimental amenability and the absence of cohesin turnover. Here, we use cultured somatic cells to unravel fundamental aspects of meiotic cohesin. When expressed in Hek293 cells, Rec8 displays no affinity for the peripheral cohesin subunits Stag1 or Stag2 and remains cytoplasmic. However, co-expression of Stag3 is sufficient for Rec8 to enter the nucleus, load onto chromatin, and functionally replace its mitotic counterpart Scc1 in cohesion and dissolution thereof. Rec8-Stag3-cohesin physically interacts with Pds5, Wapl and Sororin. Importantly, Rec8-Stag3-cohesin is shown to be susceptible to Wapl-dependent ring opening and protection by Sororin. These findings exemplify that our model system is suitable to rapidly generate testable predictions for important unresolved issues of meiotic cohesion regulation.