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Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes

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Ferrandiz, Nuria, Downie, Laura, Starling, Georgina P. and Royle, Stephen J. (2022) Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes. Journal of Cell Biology, 221 (6). e202203021. doi:10.1083/jcb.202203021

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Official URL: http://dx.doi.org/10.1083/jcb.202203021

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Abstract

Errors in mitosis that cause chromosome missegregation lead to aneuploidy and micronucleus formation, which are associated with cancer. Accurate segregation requires the alignment of all chromosomes by the mitotic spindle at the metaphase plate, and any misalignment must be corrected before anaphase is triggered. The spindle is situated in a membrane-free “exclusion zone”; beyond this zone, endomembranes (mainly endoplasmic reticulum) are densely packed. We investigated what happens to misaligned chromosomes localized beyond the exclusion zone. Here we show that such chromosomes become ensheathed in multiple layers of endomembranes. Chromosome ensheathing delays mitosis and increases the frequency of chromosome missegregation and micronucleus formation. We use an induced organelle relocalization strategy in live cells to show that clearance of endomembranes allows for the rescue of chromosomes that were destined for missegregation. Our findings indicate that endomembranes promote the missegregation of misaligned chromosomes that are outside the exclusion zone and therefore constitute a risk factor for aneuploidy.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
R Medicine > RB Pathology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Chromosomes , Mitosis, Endoplasmic reticulum , Chromosome abnormalities , Cell division , Aneuploidy
Journal or Publication Title: Journal of Cell Biology
Publisher: Rockefeller University Press
ISSN: 0021-9525
Official Date: 29 April 2022
Dates:
DateEvent
29 April 2022Published
5 April 2022Accepted
5 March 2022Submitted
Volume: 221
Number: 6
Number of Pages: 20
Article Number: e202203021
DOI: 10.1083/jcb.202203021
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
C25425/A24167Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
C25425/A27718Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
BB/M01116X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268

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