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chTOG is a conserved mitotic error correction factor
Accurate chromosome segregation requires kinetochores on duplicated chromatids to biorient by attaching to dynamic microtubules from opposite spindle poles, which exerts forces to bring kinetochores under tension. However, kinetochores initially bind to microtubules indiscriminately, resulting in er...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773332/ https://www.ncbi.nlm.nih.gov/pubmed/33377866 http://dx.doi.org/10.7554/eLife.61773 |
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author | Herman, Jacob A Miller, Matthew P Biggins, Sue |
author_facet | Herman, Jacob A Miller, Matthew P Biggins, Sue |
author_sort | Herman, Jacob A |
collection | PubMed |
description | Accurate chromosome segregation requires kinetochores on duplicated chromatids to biorient by attaching to dynamic microtubules from opposite spindle poles, which exerts forces to bring kinetochores under tension. However, kinetochores initially bind to microtubules indiscriminately, resulting in errors that must be corrected. While the Aurora B protein kinase destabilizes low-tension attachments by phosphorylating kinetochores, low-tension attachments are intrinsically less stable than those under higher tension in vitro independent of Aurora activity. Intrinsic tension-sensitive behavior requires the microtubule regulator Stu2 (budding yeast Dis1/XMAP215 ortholog), which we demonstrate here is likely a conserved function for the TOG protein family. The human TOG protein, chTOG, localizes to kinetochores independent of microtubules by interacting with Hec1. We identify a chTOG mutant that regulates microtubule dynamics but accumulates erroneous kinetochore-microtubule attachments that are not destabilized by Aurora B. Thus, TOG proteins confer a unique, intrinsic error correction activity to kinetochores that ensures accurate chromosome segregation. |
format | Online Article Text |
id | pubmed-7773332 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77733322021-01-04 chTOG is a conserved mitotic error correction factor Herman, Jacob A Miller, Matthew P Biggins, Sue eLife Cell Biology Accurate chromosome segregation requires kinetochores on duplicated chromatids to biorient by attaching to dynamic microtubules from opposite spindle poles, which exerts forces to bring kinetochores under tension. However, kinetochores initially bind to microtubules indiscriminately, resulting in errors that must be corrected. While the Aurora B protein kinase destabilizes low-tension attachments by phosphorylating kinetochores, low-tension attachments are intrinsically less stable than those under higher tension in vitro independent of Aurora activity. Intrinsic tension-sensitive behavior requires the microtubule regulator Stu2 (budding yeast Dis1/XMAP215 ortholog), which we demonstrate here is likely a conserved function for the TOG protein family. The human TOG protein, chTOG, localizes to kinetochores independent of microtubules by interacting with Hec1. We identify a chTOG mutant that regulates microtubule dynamics but accumulates erroneous kinetochore-microtubule attachments that are not destabilized by Aurora B. Thus, TOG proteins confer a unique, intrinsic error correction activity to kinetochores that ensures accurate chromosome segregation. eLife Sciences Publications, Ltd 2020-12-30 /pmc/articles/PMC7773332/ /pubmed/33377866 http://dx.doi.org/10.7554/eLife.61773 Text en © 2020, Herman et al http://creativecommons.org/licenses/by/4.0/ 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 Herman, Jacob A Miller, Matthew P Biggins, Sue chTOG is a conserved mitotic error correction factor |
title | chTOG is a conserved mitotic error correction factor |
title_full | chTOG is a conserved mitotic error correction factor |
title_fullStr | chTOG is a conserved mitotic error correction factor |
title_full_unstemmed | chTOG is a conserved mitotic error correction factor |
title_short | chTOG is a conserved mitotic error correction factor |
title_sort | chtog is a conserved mitotic error correction factor |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773332/ https://www.ncbi.nlm.nih.gov/pubmed/33377866 http://dx.doi.org/10.7554/eLife.61773 |
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