Rupes I, Webb B A, Mak A, Young P G
Departments of Biology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Mol Biol Cell. 2001 Dec;12(12):3892-903. doi: 10.1091/mbc.12.12.3892.
In budding yeast, actin disruption prevents nuclear division. This has been explained as activation of a morphogenesis checkpoint monitoring the integrity of the actin cytoskeleton. The checkpoint operates through inhibitory tyrosine phosphorylation of Cdc28, the budding yeast Cdc2 homolog. Wild-type Schizosaccharomyces pombe cells also arrest before mitosis after actin depolymerization. Oversized cells, however, enter mitosis uninhibited. We carried out a careful analysis of the kinetics of mitotic initiation after actin disruption in undersized and oversized cells. We show that an inability to reach the mitotic size threshold explains the arrest in smaller cells. Among the regulators that control the level of the inhibitory Cdc2-Tyr15 phosphorylation, the Cdc25 protein tyrosine phosphatase is required to link cell size monitoring to mitotic control. This represents a novel function of the Cdc25 phosphatase. Furthermore, we demonstrate that this cell size-monitoring system fulfills the formal criteria of a cell cycle checkpoint.
在出芽酵母中，肌动蛋白的破坏会阻止核分裂。这被解释为激活了一个监测肌动蛋白细胞骨架完整性的形态发生检查点。该检查点通过对芽殖酵母Cdc2同源物Cdc28的抑制性酪氨酸磷酸化来发挥作用。野生型粟酒裂殖酵母细胞在肌动蛋白解聚后也会在有丝分裂前停滞。然而，超大细胞不受抑制地进入有丝分裂。我们对大小不足和超大细胞中肌动蛋白破坏后有丝分裂起始的动力学进行了仔细分析。我们表明，无法达到有丝分裂大小阈值解释了较小细胞中的停滞现象。在控制抑制性Cdc2-Tyr15磷酸化水平的调节因子中，Cdc25蛋白酪氨酸磷酸酶是将细胞大小监测与有丝分裂控制联系起来所必需的。这代表了Cdc25磷酸酶的一种新功能。此外，我们证明这种细胞大小监测系统符合细胞周期检查点的形式标准。
