title: The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores.
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.
authors.affiliation: Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States.|Department of Pharmacology, University of Texas Southwestern Medical center, Dallas, United States.|Howard Hughes Medical Institute, University of Texas Southwestern Medical center, Dallas, United States.
authors.forename: Sushama
authors.initials: S
authors.lastname: Sivakumar
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: Paweł Ł
authors.initials: PŁ
authors.lastname: Janczyk
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical center, Dallas, United States.|Howard Hughes Medical Institute, University of Texas Southwestern Medical center, Dallas, United States.
authors.forename: Qianhui
authors.initials: Q
authors.lastname: Qu
authors.affiliation: Department of Biophysics, University of Texas Southwestern Medical center, Dallas, United States.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Brautigam
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
authors.forename: P Todd
authors.initials: PT
authors.lastname: Stukenberg
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical center, Dallas, United States.|Howard Hughes Medical Institute, University of Texas Southwestern Medical center, Dallas, United States.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Gary J
authors.identifier: http://orcid.org/0000-0003-3076-4725
authors.initials: GJ
authors.lastname: Gorbsky
mesh_terms: D000705:Anaphase; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008677:Metaphase; D000072417:Protein Domains; D054645:Protein Phosphatase 1 / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C516427:SKA1 protein, human; D054645:Protein Phosphatase 1
keywords: anaphase promoting complex/cyclosome; cell biology; chromosomes; genes; human; microtubule; mitosis; mps1; phosphatase; spindle checkpoint