When yeast cells change their mind: cell cycle "Start" is reversible under starvation.

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. Synopsis: If and how starvation can affect yeast cell cycle progression after commitment to division at "Start" is unclear. Here, investigation in single yeast cells shows that they can reverse this decision to a pre‐Start State upon nutrient depletion within 20 min after the canonical commitment. Yeast cells that have passed the cell cycle commitment point Start respond to acute starvation by slowing or arresting cell cycle progression.Post‐Start cells can re‐import the Start‐inhibiting repressor Whi5 into the nucleus upon starvation.After re‐importing Whi5, previously committed cells behave like pre‐Start cells again. [ABSTRACT FROM AUTHOR]