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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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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 |
format | Online Article Text |
id | pubmed-4821802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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