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

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...

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Autores principales: Sivakumar, Sushama, Janczyk, Paweł Ł, Qu, Qianhui, Brautigam, Chad A, Stukenberg, P Todd, Yu, Hongtao, Gorbsky, Gary J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821802/
https://www.ncbi.nlm.nih.gov/pubmed/26981768
http://dx.doi.org/10.7554/eLife.12902
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author Sivakumar, Sushama
Janczyk, Paweł Ł
Qu, Qianhui
Brautigam, Chad A
Stukenberg, P Todd
Yu, Hongtao
Gorbsky, Gary J
author_facet Sivakumar, Sushama
Janczyk, Paweł Ł
Qu, Qianhui
Brautigam, Chad A
Stukenberg, P Todd
Yu, Hongtao
Gorbsky, Gary J
author_sort Sivakumar, Sushama
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.12902.001
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spelling pubmed-48218022016-04-07 The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores Sivakumar, Sushama Janczyk, Paweł Ł Qu, Qianhui Brautigam, Chad A Stukenberg, P Todd Yu, Hongtao Gorbsky, Gary J eLife Cell Biology 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. DOI: http://dx.doi.org/10.7554/eLife.12902.001 eLife Sciences Publications, Ltd 2016-03-16 /pmc/articles/PMC4821802/ /pubmed/26981768 http://dx.doi.org/10.7554/eLife.12902 Text en © 2016, Sivakumar et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Sivakumar, Sushama
Janczyk, Paweł Ł
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
title The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
title_full The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
title_fullStr The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
title_full_unstemmed The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
title_short The human SKA complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
title_sort human ska complex drives the metaphase-anaphase cell cycle transition by recruiting protein phosphatase 1 to kinetochores
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821802/
https://www.ncbi.nlm.nih.gov/pubmed/26981768
http://dx.doi.org/10.7554/eLife.12902
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