During meiosis, the cohesin complexes that hold sister chromatid cohesion are lost in a stepwise manner. The cohesin subunit Rec8 is cleaved only along chromosome arms at meiosis I, while being protected at centromeres until meiosis II by the action of shugoshin (Sgo1) - protein phosphatase 2A (PP2A). Although this regulation might involve phosphorylation that is ideally antagonized by Sgo1-PP2A, the responsible kinase and substrate remain elusive. Here, by using genetic screen for ‘anti-shugoshin’, we identify Hhp2, an ortholog of casein kinase 1δ/ε (CK1), as a factor required for Rec8 cleavage in fission yeast. We show that CK1, rather than a widely believed Polo-like kinase, acts as the cohesin kinase to promote the cleavage during meiosis. Crucially, forced excess localization of Hhp2 at the pericentromeric region abrogates the ability of Sgo1-PP2A to protect centromeric Rec8. Thus, our studies prove the key notion that the balance between Rec8 phosphorylation and its dephosphorylation by Sgo1-PP2A regulate the step-wise loss of chromosomal cohesion in meiosis (Figure).

Program member
Yoshinori Watanabe (Institute of Molecular and Cellular Biosciences)

Schematic model for centromeric protection of cohesion at meiosis I. Phosphorylation of Rec8 by CK1 promotes the cleavage by separase, whereas Sgo1-PP2A counteracts this phosphorylation at centromeres, thereby preventing the cleavage of centromeric cohesin.