The human Ska complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores

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Abstract

The spindle- and kinetochore-associated (Ska) complex is essential for normal anaphase onset in mitosis. The C-terminal domain (CTD) of Ska1 binds microtubules and was proposed to facilitate kinetochore movement on depolymerizing spindle microtubules. Here we show that Ska complex recruits protein phosphatase 1 (PP1) to kinetochores. This recruitment requires the Ska1 CTD, which binds PP1 in vitro and in human HeLa cells. Ska1 lacking its CTD fused to a PP1-binding peptide or fused directly to PP1 rescues mitotic defects caused by Ska1 depletion. Ska1 fusion to catalytically dead PP1 mutant does not rescue and shows dominant negative effects. Thus, the Ska complex, specifically the Ska1 CTD, recruits PP1 to kinetochores to oppose spindle checkpoint signaling kinases and promote anaphase onset. Microtubule binding by Ska, rather than acting in force production for chromosome movement, may instead serve to promote PP1 recruitment to kinetochores fully attached to spindle microtubules at metaphase.

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Sushama Sivakumar

Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States

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The authors declare that no competing interests exist.
Paweł Ł Janczyk

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States

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The authors declare that no competing interests exist.
Qianhui Qu

Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical center, Dallas, United States

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The authors declare that no competing interests exist.
Chad A Brautigam

Department of Biophysics, University of Texas Southwestern Medical center, Dallas, United States

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The authors declare that no competing interests exist.
P Todd Stukenberg

Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States

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The authors declare that no competing interests exist.
Hongtao Yu

Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical center, Dallas, United States

Competing interests
The authors declare that no competing interests exist.
Gary J Gorbsky

Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States

For correspondence
GJG@omrf.org

Competing interests
The authors declare that no competing interests exist.

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