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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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Official URL: https://doi.org/10.1016/j.devcel.2021.10.007

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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
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
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:
DateEvent
22 November 2021Published
9 November 2021Available
6 October 2021Accepted
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:
Project/Grant IDRIOXX Funder NameFunder ID
208384/Z/17/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
BB/R009503/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
106151/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269

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