Letter abstract

Nature Cell Biology 12, 500 - 506 (2010)
Published online: 11 April 2010 | doi:10.1038/ncb2052

Shugoshin–PP2A counteracts casein-kinase-1-dependent cleavage of Rec8 by separase

Tadashi Ishiguro1,2, Koichi Tanaka1, Takeshi Sakuno1,3 & Yoshinori Watanabe1,2


During meiosis, the cohesin complexes that maintain sister chromatid cohesion are lost in a stepwise manner1, 2. At meiosis I the cohesin subunit Rec8 is cleaved only along the chromosome arms; until meiosis II it is protected at centromeres by the action of shugoshin (Sgo1)–protein phosphatase 2A (PP2A)3, 4, 5. Although this regulation hypothetically involves phosphorylation that is antagonized by Sgo1–PP2A, the kinase and substrate that are responsible are as yet unknown6, 7. Using a genetic screen for 'anti-shugoshin', we identify Hhp2, an orthologue of casein kinase 1δ/ε (CK1), as a factor required for Rec8 cleavage in fission yeast. We show that CK1, rather than a Polo-like kinase that is widely believed to do so, acts as the cohesin kinase to promote this cleavage during meiosis. Crucially, forced localization of excess 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 regulates the step-wise loss of chromosomal cohesion in meiosis.

  1. Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
  2. Graduate Program in Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.
  3. Promotion of Independence for Young Investigators, University of Tokyo, Yayoi, Tokyo 113-0032, Japan.

Correspondence to: Yoshinori Watanabe1,2 e-mail: ywatanab@iam.u-tokyo.ac.jp


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