Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes.
Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes.
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内膜通过包裹排列不齐的染色体促进染色体的错误分离。
DOI：
10.1083/jcb.202203021
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发表时间：
2022-06-06
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
作者：
Ferrandiz等人发现，由有丝分裂中的错误引起的染色体错位，可以在内膜中被“包裹”。鞘化使染色体偏向错误分离，导致非整倍体和微核形成。作者使用了一种新的方法来去除鞘膜，这使得纺锤体能够拯救染色体。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，这与癌症有关。准确的分离需要所有染色体在中期板上通过有丝分裂纺锤体对齐，并且任何不对齐都必须在后期触发之前纠正。纺锤体位于一个无膜的“禁区”，在禁区外，内膜（主要是内质网）密集。我们研究了排除区以外的染色体错位会发生什么。在这里，我们表明，这样的染色体成为套在多层内膜。染色体鞘化延迟有丝分裂，增加染色体错分离和微核形成的频率。我们在活细胞中使用诱导的细胞器重新定位策略来表明内膜的清除允许拯救注定要错误分离的染色体。我们的研究结果表明，内膜促进了排异区以外的染色体的错误分离，因此构成了非整倍体的风险因素。
Ferrandiz et al. found that misaligned chromosomes, arising from errors in mitosis, can become “ensheathed” in endomembranes. Ensheathing biases chromosomes toward missegregation, leading to aneuploidy and micronucleus formation. The authors use a novel method to remove the ensheathing membranes, which allows the spindle to rescue the chromosome. 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.
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影响因子：
11.8
作者：
Funk LC;Zasadil LM;Weaver BA
通讯作者：
Weaver BA
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
3.7
作者：
BAJER, A
通讯作者：
BAJER, A
DOI：
10.1083/jcb.201012063
发表时间：
2011-08-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lu L;Ladinsky MS;Kirchhausen T
通讯作者：
Kirchhausen T