Proliferation/Quiescence: When to start? Where to stop? What to stock?

The restriction point is defined as a point in G1 phase of the cell cycle after which cells are committed to cell division [1]. Indeed, it is commonly accepted that once cells have passed this point, they proceed through all the phases of the cell cycle until completion, i.e. until they reach the restriction point again. But cells may individually "decide" to engage themselves in another round of cell division or enter a non-dividing state. This non-dividing state may be non-reversible (senescence, apoptosis...) or, alternatively, cells can enter quiescence, a cellular state defined as a temporary and reversible absence of proliferation. In all cases, it is thought that cells integrate a combination of external and internal signals before committing to the cell division cycle. In multi-cellular eukaryotes, external signals emanate from the entire organism. These extremely complex physiological conditions are difficult to reproduce in a laboratory. By contrast, in single cell eukaryotes like budding yeast, these external cues can be easily monitored since entry into-and exit from the cell cycle apparently rely solely on nutrient availability in the growth medium. As mammalian cells, yeast cells, once they have passed a point called Start (originally defined as a point in G1 after which cells are resistant to mating pheromone [2]) are committed to proceed through all the phases of the cell cycle until G1 [3].The molecular nature of Start has been extensively investigated and a fair amount of key proteins, including cyclins and cyclin-dependent kinases, together with crucial signalling networks have been discovered. However, in yeast, as in metazoa, how these regulators integrate external and internal signals to trigger either the re-entry into the cell cycle or the transition to non-dividing cellular states remains largely mysterious.Recently, using budding yeast as a model organism, transitions from proliferation to quiescence have been revisited by means of several