Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes

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.

Automated summary

Misalignment of chromosomes during mitosis can result in chromosome missegregation and the formation of micronuclei, which are associated with cancer. A study showed that chromosomes located beyond the exclusion zone become ensheathed in multiple layers of endomembranes, leading to delayed mitosis and increased frequency of chromosome missegregation and micronucleus formation. Clearance of endomembranes can rescue those chromosomes that were destined for missegregation, indicating that endomembranes promote the missegregation of misaligned chromosomes outside the exclusion zone and pose a risk factor for aneuploidy.