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

Sushama Sivakumar, Paweł Janczyk, Qianhui Qu, Chad A. Brautigam, P. Todd Stukenberg, Hongtao Yu, Gary J. Gorbsky

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere12902
JournaleLife
Volume5
Issue numberMARCH2016
DOIs
StatePublished - Mar 16 2016

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Protein Phosphatase 1
Kinetochores
Anaphase
Metaphase
Cell Cycle
Cells
Microtubules
Chromosomes
HeLa Cells
Mitosis
Phosphotransferases
Fusion reactions
Defects
Peptides

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores. / Sivakumar, Sushama; Janczyk, Paweł; Qu, Qianhui; Brautigam, Chad A.; Stukenberg, P. Todd; Yu, Hongtao; Gorbsky, Gary J.

In: eLife, Vol. 5, No. MARCH2016, e12902, 16.03.2016.

Research output: Contribution to journalArticle

Sivakumar, Sushama ; Janczyk, Paweł ; Qu, Qianhui ; Brautigam, Chad A. ; Stukenberg, P. Todd ; Yu, Hongtao ; Gorbsky, Gary J. / The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores. In: eLife. 2016 ; Vol. 5, No. MARCH2016.
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