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

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Wolf, Peter G. ; Ramos, Alexander Cuba ; Kenzel, Julia ; Neumann, Brigitte ; Stemmann, Olaf:
Studying meiotic cohesin in somatic cells reveals that Rec8-containing cohesin requires Stag3 to function and is regulated by Wapl and sororin.
In: Journal of Cell Science. Bd. 131 (2018) Heft 11 . - jcs.212100.
ISSN 1477-9137
DOI: https://doi.org/10.1242/jcs.212100

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Abstract

The DNA-embracing, ring-shaped multiprotein complex cohesin mediates sister chromatid cohesion and is stepwise displaced in mitosis by Wapl and separase (also known as ESPL1) to facilitate anaphase. Proper regulation of chromosome cohesion throughout meiosis is critical for preventing 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, the kleisin 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 (also known as RAD21) during sister chromatid cohesion and dissolution. Rec8-Stag3 cohesin physically interacts with Pds5, Wapl and sororin (also known as CDCA5). Importantly, Rec8-Stag3 cohesin is shown to be susceptible to Wapl-dependent ring opening and sororin-mediated protection. These findings exemplify that our model system is suitable to rapidly generate testable predictions for important unresolved issues of meiotic cohesion regulation.