Mechanisms of Chromosome biorientation and bipolar spindle assembly analyzed by computational modeling
Mechanisms of Chromosome biorientation and bipolar spindle assembly analyzed by computational modeling
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DOI：
10.7554/elife.48787
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发表时间：
2020-02-13
期刊：
影响因子：
7.7
通讯作者：
Betterton, Meredith D.
中科院分区：
文献类型：
--
作者：
Edelmaier, Christopher;Lamson, Adam R.;Betterton, Meredith D.
有丝分裂纺锤体组装和染色体双向定位和分离所需的基本功能尚未完全了解，尽管广泛的研究。为了阐明对染色体排列和分离以及同时组装双极纺锤体最重要的成分组合，我们开发了一个分裂酵母有丝分裂的计算模型。稳健的染色体双取向需要渐进的限制附件的几何形状，不稳定的错位附件，和附着力的依赖性。大的纺锤体长度波动时，可能会发生的着丝粒微管附着寿命长。在有丝分裂早期，主轴力的产生者是驱动蛋白-5马达和交联剂，而在双取向后，动粒间拉伸变得重要。同样的机制，有助于持久的双取向导致分离的染色体的两极后，后期开始。因此，该模型提供了一个框架来询问稳健的染色体双向取向、纺锤体长度调节和纺锤体中力产生的关键要求。
The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood, despite extensive study. To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle, we developed a computational model of fission-yeast mitosis. Robust chromosome biorientation requires progressive restriction of attachment geometry, destabilization of misaligned attachments, and attachment force dependence. Large spindle length fluctuations can occur when the kinetochore-microtubule attachment lifetime is long. The primary spindle force generators are kinesin-5 motors and crosslinkers in early mitosis, while interkinetochore stretch becomes important after biorientation. The same mechanisms that contribute to persistent biorientation lead to segregation of chromosomes to the poles after anaphase onset. This model therefore provides a framework to interrogate key requirements for robust chromosome biorientation, spindle length regulation, and force generation in the spindle.