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.

中文翻译：

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内膜通过包裹错位的染色体来促进染色体错分

有丝分裂中的错误导致染色体错误分离，导致非整倍体和微核形成，这与癌症相关。准确的分离需要通过中期板的有丝分裂纺锤体对齐所有染色体，并且必须在触发后期之前纠正任何错位。纺锤体位于无膜“禁区”；超出该区域，内膜（主要是内质网）密集。我们研究了位于禁区之外的错位染色体会发生什么情况。在这里，我们证明这些染色体被多层内膜包裹。染色体鞘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来证明内膜的清除可以挽救注定错误分离的染色体。我们的研究结果表明，内膜促进了禁区之外的错位染色体的错误分离，因此构成了非整倍体的危险因素。