Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, USA; Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24061, USA; Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tuebingen, Germany.
Institute of Molecular Biology (IMB), 55128 Mainz, Germany.
Mol Cell. 2015 Nov 5;60(3):446-59. doi: 10.1016/j.molcel.2015.09.022. Epub 2015 Oct 29.
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.
在后期，染色体的分裂及其分配到子细胞中需要准确执行，以维持基因组的稳定性。染色体的分裂需要 securin 的降解，而染色体分配到子细胞中则需要 cyclin B 的降解。我们表明，细胞会遇到并耐受 securin 或 cyclin B 丰度的变化。这使得 securin 和 cyclin B 降解的同时发生不足以保证早期后期事件按正确的顺序发生。我们发现，染色体分裂的时间不是由达到固定的 securin 水平决定的，而是该水平适应 securin 降解动力学。与 securin 和 cyclin B 在后期竞争降解相结合，这为后期事件的时间顺序提供了稳健性。我们的工作揭示了尽管蛋白质浓度存在变异性，但平行的细胞周期途径如何在时间上协调。
