Robust Ordering of Anaphase Events by Adaptive Thresholds and Competing Degradation Pathways
Robust Ordering of Anaphase Events by Adaptive Thresholds and Competing Degradation Pathways
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DOI：
10.1016/j.molcel.2015.09.022
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发表时间：
2015-11-05
期刊：
影响因子：
16
通讯作者：
Hauf, Silke
中科院分区：
文献类型：
--
作者：
Kamenz, Julia;Mihaljev, Tamara;Hauf, Silke
染色体在后期的分裂和它们进入子细胞的传递需要精确地执行，以保持基因组的稳定性。染色体分裂需要安全蛋白的降解，而染色体在子细胞中的分布需要周期蛋白B的降解。我们发现细胞会遇到并容忍安全蛋白或周期蛋白B丰度的变化，这使得安全蛋白和周期蛋白B降解的同时发生不足以保证早期后期事件以正确的顺序发生。我们发现染色体分裂的时间不是由达到一个固定的安全蛋白水平决定的，而是这个水平与安全蛋白降解动力学相适应。结合securin和cyclin B在后期竞争降解，这为后期事件的时间顺序提供了鲁棒性。我们的工作揭示了平行的细胞周期途径如何在蛋白质浓度变化的情况下暂时协调。
The splitting of chromosomes in anaphase and their delivery into the daughter cells needs to be accurately executed to maintain genome stability. Chromosome splitting requires the degradation of securin, whereas the distribution of the chromosomes into the daughter cells requires the degradation of cyclin B. We show that cells encounter and tolerate variations in the abundance of securin or cyclin B. This makes the concurrent onset of securin and cyclin B degradation insufficient to guarantee that early anaphase events occur in the correct order. We uncover that the timing of chromosome splitting is not determined by reaching a fixed securin level, but that this level adapts to the securin degradation kinetics. In conjunction with securin and cyclin B competing for degradation during anaphase, this provides robustness to the temporal order of anaphase events. Our work reveals how parallel cell-cycle pathways can be temporally coordinated despite variability in protein concentrations.