Multiple inputs ensure yeast cell size homeostasis during cell cycle progression.

Cecilia Garmendia-Torres,Gilles Charvin,Olivier Tassy,Nacho Molina,Audrey Matifas

doi:10.7554/elife.34025

Abstract

Coordination of cell growth with division is essential for proper cell function. In budding yeast, although some molecular mechanisms responsible for cell size control during G1 have been elucidated, the mechanism by which cell size homeostasis is established remains to be discovered. Here, we developed a new technique based on quantification of histone levels to monitor cell cycle progression in individual cells with unprecedented accuracy. Our analysis establishes the existence of a mechanism controlling bud size in G2/M that prevents premature onset of anaphase, and controls the overall size variability. While most G1 mutants do not display impaired size homeostasis, mutants in which cyclin B-Cdk regulation is altered display large size variability. Our study thus demonstrates that size homeostasis is not controlled by a G1-specific mechanism alone but is likely to be an emergent property resulting from the integration of several mechanisms that coordinate cell and bud growth with division.

Highlights

To ensure cell size homeostasis, cells must coordinate growth and division during the mitotic cycle
A ‘Sizer’ mechanism has been shown to operate in yeast: the transition to a given cell cycle phase occurs when cells have attained a critical size during the preceding phase
We reasoned that the burst of histone synthesis could serve as an accurate marker of S phase, thanks to the tight reciprocal coupling of DNA replication and histone synthesis, which has been characterized in detail (Baumbach et al, 1987; Heintz et al, 1983; Nelson et al, 2002; Sittman et al, 1983)

Summary

Introduction

To ensure cell size homeostasis, cells must coordinate growth and division during the mitotic cycle. In a free-running cell cycle oscillator model (i.e. in the absence of any coupling to control signals, such as cell size), the cell division time is set by the sum of fixed intervals associated with successive cell cycle events (referred to as ‘Timer’). In this case, the absence of coordination between the cell cycle engine and cell growth may induce deleterious fluctuations in cell size. Small cells experience a size-dependent cell cycle delay and a compensatory mass addition works as a counteracting force to restore size equilibrium

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Conclusion