Eukaryotic cells decide in late G1 phase of the cell cycle whether to commit to another round of division. This point of cell cycle commitment is termed “Restriction Point” in mammals and “Start” in the budding yeast Saccharomyces cerevisiae. At Start, yeast cells integrate multiple signals such as pheromones and nutrients, and will not pass Start if nutrients are lacking. However, how cells respond to nutrient depletion after the Start decision remains poorly understood. Here, we analyze how post-Start cells respond to nutrient depletion, by monitoring Whi5, the cell cycle inhibitor whose export from the nucleus determines Start. Surprisingly, we find that cells that have passed Start can re-import Whi5 into the nucleus. In these cells, the positive feedback loop activating G1/S transcription is interrupted, and the Whi5 repressor re-binds DNA. Cells which re-import Whi5 become again sensitive to mating pheromone, like pre-Start cells, and CDK activation can occur a second time upon replenishment of nutrients. These results demonstrate that upon starvation, the commitment decision at Start can be reversed. We therefore propose that cell cycle commitment in yeast is a multi-step process, similar to what has been suggested for mammalian cells.

中文翻译：

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当酵母细胞改变主意时：细胞周期“开始”在饥饿条件下是可逆的

真核细胞在细胞周期的 G1 后期决定是否进行另一轮分裂。这个细胞周期定型点在哺乳动物中被称为“限制点”，在出芽酵母酿酒酵母中被称为“起始点”。在Start，酵母细胞整合了信息素和营养素等多种信号，如果缺乏营养素，酵母细胞将无法通过Start。然而，细胞如何在开始决定后对营养耗尽作出反应仍然知之甚少。在这里，我们通过监测 Whi5 来分析启动后细胞如何对营养耗尽做出反应，Whi5 是一种细胞周期抑制剂，其从细胞核中的输出决定启动。令人惊讶的是，我们发现通过 Start 的细胞可以重新-将 Whi5 导入细胞核。在这些细胞中，激活 G1/S 转录的正反馈环被中断，Whi5 阻遏物重新结合 DNA。重新导入 Whi5 的细胞再次对交配信息素敏感，如启动前细胞，CDK 激活可在补充营养后第二次发生。这些结果表明，在饥饿时，开始时的承诺决定可以逆转。因此，我们提出酵母中的细胞周期定型是一个多步骤过程，类似于对哺乳动物细胞的建议。