Chromosome size-dependent polar ejection force impairs mammalian mitotic error correction.
Chromosome size-dependent polar ejection force impairs mammalian mitotic error correction.
复制标题
染色体大小依赖性极喷射力损害哺乳动物有丝分裂纠错。
DOI：
10.1101/2023.10.16.562637
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Dumont,Sophie
中科院分区：
文献类型：
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作者：
Chong,MeganK;Rosas-Salvans,Miquel;Tran,Vanna;Dumont,Sophie
准确的染色体分离需要姐妹动粒双定向，连接到相反的纺锤体两极。为此，哺乳动物动粒使不正确的附着不稳定，使正确的附着稳定，但它如何区分这些附着尚不清楚。在这里，我们测试的模型，动粒张力是稳定的线索，并询问染色体大小如何影响该模型。我们对PtK2细胞进行了实时成像，该细胞只有14条染色体，大小范围很广，并且发现长染色体在中期板上的排列晚于短染色体。丰富的错误和成像误差校正生活，我们表明，长染色体表现出特定的延迟，在纠正附件。使用chromokinesin过表达和激光消融扰动极性弹射力，我们发现，染色体的大小和力的武器决定对齐顺序。因此，我们提出了一个模型，其中长染色体上的力增加可以错误地稳定不正确的附件，延迟它们的双取向。因此，长染色体可能需要补偿机制来纠正错误以避免染色体不稳定性。
Accurate chromosome segregation requires sister kinetochores to biorient, attaching to opposite spindle poles. To this end, the mammalian kinetochore destabilizes incorrect attachments and stabilizes correct ones, but how it discriminates between these is not yet clear. Here, we test the model that kinetochore tension is the stabilizing cue and ask how chromosome size impacts that model. We live image PtK2 cells, with just 14 chromosomes, widely ranging in size, and find that long chromosomes align at the metaphase plate later than short chromosomes. Enriching for errors and imaging error correction live, we show that long chromosomes exhibit a specific delay in correcting attachments. Using chromokinesin overexpression and laser ablation to perturb polar ejection forces, we find that chromosome size and force on arms determine alignment order. Thus, we propose a model where increased force on long chromosomes can falsely stabilize incorrect attachments, delaying their biorientation. As such, long chromosomes may require compensatory mechanisms for correcting errors to avoid chromosomal instability.