Abstract
The cell cycle is a tightly controlled series of events that ultimately lead to cell division. The literature deciphering the molecular processes involved in regulating the consecutive cell cycle steps is colossal. By contrast, much less is known about non-dividing cellular states, even if they concern the vast majority of cells, from prokaryotes to multi-cellular organisms. Indeed, cells decide to enter the division cycle only if conditions are favourable. Otherwise they may enter quiescence, a reversible non-dividing cellular state. Recent studies in yeast have shed new light on the transition between proliferation and quiescence, re-questioning the notion of cell cycle commitment. They also indicate a predominant role for cellular metabolic status as a major regulator of quiescence establishment and exit. Additionally, a growing body of evidence indicates that environmental conditions, and notably the availability of various nutrients, by impinging on specific metabolic routes, directly regulate specific cellular re-organization that occurs upon proliferation/quiescence transitions.
Highlights
The restriction point is defined as a point in G1 phase of the cell cycle after which cells are committed to cell division [1]
It becomes more and more clear that, very helpful to decipher the highly complex network of proteins involved in cell cycle regulation, the simplistic “fence model” most probably does not reflect what happens in a physiological context, where both internal and external signals need to be integrated for the decision to enter or not a new round of cell division
Where to stop? If cells can enter quiescence in various cell cycle stages, why do budding yeast and mammalian cells preferentially do so in G1? Could it be that quiescence establishment in G1 provides a selective advantage? In agreement with this hypothesis, we have shown that in S. cerevisiae, the ability to give rise to progeny of quiescent cells arrested in other phases than G1 is somehow diminished compared to those arrested in G1 [7]
Summary
The restriction point is defined as a point in G1 phase of the cell cycle after which cells are committed to cell division [1]. In yeast, as in metazoa, how these regulators integrate external and internal signals to trigger either the reentry into the cell cycle or the transition to non-dividing cellular states remains largely mysterious. Using budding yeast as a model organism, transitions from proliferation to quiescence have been revisited by means of several powerful “omic” approaches and at the individual cell level [4,5,6,7]. These studies have re-questioned the existence of a quiescence program, an issue that we have recently discussed elsewhere [8]. These studies, centered on quiescence, shed new light on the notion of Start, cell cycle commitment and cell cycle progression
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