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Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase
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Sen, Onur, Harrison, Jonathan, Burroughs, Nigel John and McAinsh, Andrew D. (2021) Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase. Developmental Cell, 56 (22). pp. 3082-3099. doi:10.1016/j.devcel.2021.10.007
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WRAP-Kinetochore-life-histories-reveal-Aurora-B-dependent-error-correction-mechanism-anaphase-2021.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (8Mb) | Preview |
Official URL: https://doi.org/10.1016/j.devcel.2021.10.007
Abstract
Chromosome mis-segregation during mitosis leads to aneuploidy, which is a hallmark of cancer and linked to cancer genome evolution. Errors can manifest as "lagging chromosomes" in anaphase, although their mechanistic origins and likelihood of correction are incompletely understood. Here, we combine lattice light-sheet microscopy, endogenous protein labeling, and computational analysis to define the life history of >10 kinetochores. By defining the "laziness" of kinetochores in anaphase, we reveal that chromosomes are at a considerable risk of mis-segregation. We show that the majority of lazy kinetochores are corrected rapidly in anaphase by Aurora B; if uncorrected, they result in a higher rate of micronuclei formation. Quantitative analyses of the kinetochore life histories reveal a dynamic signature of metaphase kinetochore oscillations that forecasts their anaphase fate. We propose that in diploid human cells chromosome segregation is fundamentally error prone, with an additional layer of anaphase error correction required for stable karyotype propagation.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QH Natural history | ||||||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science > Mathematics Faculty of Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Human chromosomes, Cell organelles , Aneuploidy | ||||||||||||
| Journal or Publication Title: | Developmental Cell | ||||||||||||
| Publisher: | Cell Press | ||||||||||||
| ISSN: | 1534-5807 | ||||||||||||
| Official Date: | 22 November 2021 | ||||||||||||
| Dates: |
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| Volume: | 56 | ||||||||||||
| Number: | 22 | ||||||||||||
| Page Range: | pp. 3082-3099 | ||||||||||||
| DOI: | 10.1016/j.devcel.2021.10.007 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||
| Copyright Holders: | Crown Copyright © 2021 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) | ||||||||||||
| RIOXX Funder/Project Grant: |
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