Centre for Mechanochemical Cell Biology, Warwick Medical School, Coventry, UK.
J Cell Biol. 2022 Jun 6;221(6). doi: 10.1083/jcb.202203021. Epub 2022 Apr 29.
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.
有丝分裂过程中的错误会导致染色体错误分离，从而形成非整倍体和微核，这与癌症有关。准确的分离需要有丝分裂纺锤体在中期板上排列所有染色体，如果在触发后期之前没有纠正任何错误的排列，就必须进行纠正。纺锤体位于一个没有膜的“排斥区”；在这个区域之外，内膜（主要是内质网）密集排列。我们研究了位于排斥区之外的错位染色体会发生什么情况。在这里，我们发现这些染色体被多层内膜包裹。染色体被包裹会延迟有丝分裂，并增加染色体错误分离和微核形成的频率。我们在活细胞中使用诱导细胞器重定位策略表明，内膜的清除可以挽救那些注定要发生错误分离的染色体。我们的研究结果表明，内膜促进了位于排斥区之外的错位染色体的错误分离，因此是非整倍体的一个风险因素。
