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Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation
The spindle assembly checkpoint (SAC) relies on the recruitment of Mad1-C-Mad2 to unattached kinetochores but also on its binding to Megator/Tpr at nuclear pore complexes (NPCs) during interphase. However, the molecular underpinnings controlling the spatiotemporal redistribution of Mad1-C-Mad2 as ce...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054998/ https://www.ncbi.nlm.nih.gov/pubmed/31913420 http://dx.doi.org/10.1083/jcb.201906039 |
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author | Cunha-Silva, Sofia Osswald, Mariana Goemann, Jana Barbosa, João Santos, Luis M. Resende, Pedro Bange, Tanja Ferrás, Cristina Sunkel, Claudio E. Conde, Carlos |
author_facet | Cunha-Silva, Sofia Osswald, Mariana Goemann, Jana Barbosa, João Santos, Luis M. Resende, Pedro Bange, Tanja Ferrás, Cristina Sunkel, Claudio E. Conde, Carlos |
author_sort | Cunha-Silva, Sofia |
collection | PubMed |
description | The spindle assembly checkpoint (SAC) relies on the recruitment of Mad1-C-Mad2 to unattached kinetochores but also on its binding to Megator/Tpr at nuclear pore complexes (NPCs) during interphase. However, the molecular underpinnings controlling the spatiotemporal redistribution of Mad1-C-Mad2 as cells progress into mitosis remain elusive. Here, we show that activation of Mps1 during prophase triggers Mad1 release from NPCs and that this is required for kinetochore localization of Mad1-C-Mad2 and robust SAC signaling. We find that Mps1 phosphorylates Megator/Tpr to reduce its interaction with Mad1 in vitro and in Drosophila cells. Importantly, preventing Mad1 from binding to Megator/Tpr restores Mad1 accumulation at kinetochores, the fidelity of chromosome segregation, and genome stability in larval neuroblasts of mps1-null mutants. Our findings demonstrate that the subcellular localization of Mad1 is tightly coordinated with cell cycle progression by kinetochore-extrinsic activity of Mps1. This ensures that both NPCs in interphase and kinetochores in mitosis can generate anaphase inhibitors to efficiently preserve genomic stability. |
format | Online Article Text |
id | pubmed-7054998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70549982020-09-02 Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation Cunha-Silva, Sofia Osswald, Mariana Goemann, Jana Barbosa, João Santos, Luis M. Resende, Pedro Bange, Tanja Ferrás, Cristina Sunkel, Claudio E. Conde, Carlos J Cell Biol Report The spindle assembly checkpoint (SAC) relies on the recruitment of Mad1-C-Mad2 to unattached kinetochores but also on its binding to Megator/Tpr at nuclear pore complexes (NPCs) during interphase. However, the molecular underpinnings controlling the spatiotemporal redistribution of Mad1-C-Mad2 as cells progress into mitosis remain elusive. Here, we show that activation of Mps1 during prophase triggers Mad1 release from NPCs and that this is required for kinetochore localization of Mad1-C-Mad2 and robust SAC signaling. We find that Mps1 phosphorylates Megator/Tpr to reduce its interaction with Mad1 in vitro and in Drosophila cells. Importantly, preventing Mad1 from binding to Megator/Tpr restores Mad1 accumulation at kinetochores, the fidelity of chromosome segregation, and genome stability in larval neuroblasts of mps1-null mutants. Our findings demonstrate that the subcellular localization of Mad1 is tightly coordinated with cell cycle progression by kinetochore-extrinsic activity of Mps1. This ensures that both NPCs in interphase and kinetochores in mitosis can generate anaphase inhibitors to efficiently preserve genomic stability. Rockefeller University Press 2020-01-08 /pmc/articles/PMC7054998/ /pubmed/31913420 http://dx.doi.org/10.1083/jcb.201906039 Text en © 2020 Cunha-Silva et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Report Cunha-Silva, Sofia Osswald, Mariana Goemann, Jana Barbosa, João Santos, Luis M. Resende, Pedro Bange, Tanja Ferrás, Cristina Sunkel, Claudio E. Conde, Carlos Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation |
title | Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation |
title_full | Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation |
title_fullStr | Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation |
title_full_unstemmed | Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation |
title_short | Mps1-mediated release of Mad1 from nuclear pores ensures the fidelity of chromosome segregation |
title_sort | mps1-mediated release of mad1 from nuclear pores ensures the fidelity of chromosome segregation |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054998/ https://www.ncbi.nlm.nih.gov/pubmed/31913420 http://dx.doi.org/10.1083/jcb.201906039 |
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