Istituto Firc di Oncologia Molecolare, IFOM, via Adamello 16, 20139 Milan, Italy.
Istituto Firc di Oncologia Molecolare, IFOM, via Adamello 16, 20139 Milan, Italy; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.
Curr Biol. 2018 Jan 8;28(1):28-37.e7. doi: 10.1016/j.cub.2017.11.031. Epub 2017 Dec 14.
Improperly attached chromosomes activate the mitotic checkpoint that arrests cell division before anaphase. Cells can maintain an arrest for several hours but eventually will resume proliferation, a process we refer to as adaptation. Whether adapting cells bypass an active block or whether the block has to be removed to resume proliferation is not clear. Likewise, it is not known whether all cells of a genetically homogeneous population are equally capable to adapt. Here, we show that the mitotic checkpoint is operational when yeast cells adapt and that each cell has the same propensity to adapt. Our results are consistent with a model of the mitotic checkpoint where adaptation is driven by random fluctuations of APC/C, the molecular species inhibited by the checkpoint. Our data provide a quantitative framework for understanding how cells overcome a constant stimulus that halts cell cycle progression.
染色体连接不当会激活有丝分裂检查点，在后期开始前阻止细胞分裂。细胞可以维持数小时的阻滞，但最终会恢复增殖，我们称之为适应。目前尚不清楚适应细胞是绕过活跃的阻滞还是必须去除阻滞才能恢复增殖。同样，也不清楚遗传同质群体的所有细胞是否都具有同等的适应能力。在这里，我们表明当酵母细胞适应时，有丝分裂检查点是起作用的，并且每个细胞都有相同的适应倾向。我们的结果与 APC/C 驱动的有丝分裂检查点模型一致，该模型受检查点抑制的分子物种。我们的数据为理解细胞如何克服阻止细胞周期进程的恒定刺激提供了一个定量框架。
