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Updated: Sep 25, 2025

Live Cell Imaging of Chromosome Segregation During Mitosis
Published on: March 14, 2018
Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes
Nuria Ferrandiz1, Laura Downie1, Georgina P Starling1
1Centre for Mechanochemical Cell Biology, Warwick Medical School, Coventry, UK.
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.
Insights
Misaligned chromosomes outside the mitotic spindle
Area of Science:
- Cell biology
- Cancer research
- Genetics
Background:
- Chromosome missegregation during mitosis causes aneuploidy and micronucleus formation, linked to cancer.
- Proper chromosome alignment by the mitotic spindle is crucial for accurate cell division.
- Endomembranes, primarily endoplasmic reticulum, are densely packed outside the spindle's exclusion zone.
Purpose of the Study:
- To investigate the fate of misaligned chromosomes located beyond the spindle exclusion zone.
- To determine the role of endomembranes in chromosome missegregation.
- To explore therapeutic strategies for preventing aneuploidy.
Main Methods:
- Live-cell imaging to observe chromosome behavior and endomembrane interactions.
- Induced organelle relocalization to manipulate endomembrane proximity to chromosomes.
- Analysis of chromosome missegregation and micronucleus formation frequencies.
Main Results:
- Misaligned chromosomes outside the exclusion zone become ensheathed in multiple endomembrane layers.
- Endomembrane ensheathing delays mitosis and increases chromosome missegregation and micronucleus formation.
- Clearance of endomembranes rescues missegregated chromosomes, reducing aneuploidy risk.
Conclusions:
- Endomembranes promote the missegregation of misaligned chromosomes outside the spindle exclusion zone.
- Endomembrane accumulation near chromosomes is a risk factor for aneuploidy.
- Targeting endomembrane interactions could offer novel cancer therapeutic approaches.
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