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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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WRAP-Endomembranes-promote-chromosome-missegregation-by-ensheathing-misaligned-chromosomes-Royle-22.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (6Mb) | Preview |
Official URL: http://dx.doi.org/10.1083/jcb.202203021
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 | ||||||||||||
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| Subjects: | Q Science > QH Natural history R Medicine > RB Pathology |
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| 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 |
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| 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 | ||||||||||||
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| 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: |
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