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Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation
The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore–microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalli...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963475/ https://www.ncbi.nlm.nih.gov/pubmed/27457023 http://dx.doi.org/10.1038/ncomms12256 |
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author | Zhang, Gang Mendez, Blanca Lopez Sedgwick, Garry G. Nilsson, Jakob |
author_facet | Zhang, Gang Mendez, Blanca Lopez Sedgwick, Garry G. Nilsson, Jakob |
author_sort | Zhang, Gang |
collection | PubMed |
description | The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore–microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore–microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3. |
format | Online Article Text |
id | pubmed-4963475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49634752016-09-06 Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation Zhang, Gang Mendez, Blanca Lopez Sedgwick, Garry G. Nilsson, Jakob Nat Commun Article The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore–microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signalling or only contributes to kinetochore–microtubule interactions is debated. Here we show that two distinct pools of BubR1/Bub3 exist at kinetochores and we uncouple these with defined BubR1/Bub3 mutants to address their function. The major kinetochore pool of BubR1/Bub3 is dependent on direct Bub1/Bub3 binding and is required for chromosome alignment but not for the SAC. A distinct pool of BubR1/Bub3 localizes by directly binding to phosphorylated MELT repeats on the outer kinetochore protein KNL1. When we prevent the direct binding of BubR1/Bub3 to KNL1 the checkpoint is weakened because BubR1/Bub3 is not incorporated into checkpoint complexes efficiently. In conclusion, kinetochore localization supports both known functions of BubR1/Bub3. Nature Publishing Group 2016-07-26 /pmc/articles/PMC4963475/ /pubmed/27457023 http://dx.doi.org/10.1038/ncomms12256 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhang, Gang Mendez, Blanca Lopez Sedgwick, Garry G. Nilsson, Jakob Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation |
title | Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation |
title_full | Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation |
title_fullStr | Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation |
title_full_unstemmed | Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation |
title_short | Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation |
title_sort | two functionally distinct kinetochore pools of bubr1 ensure accurate chromosome segregation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963475/ https://www.ncbi.nlm.nih.gov/pubmed/27457023 http://dx.doi.org/10.1038/ncomms12256 |
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