A Size-invariant Bud-length Timer Enables Robustness in Yeast Cell Size Control

Abstract

Precise control of cell size is evident across nearly all forms of life. Many cellular components, including DNA and organelles, display a strong positive correlation with cell size, and maintenance of uniform size may underlie the efficient functioning of tissues and organs. Prior work has uncovered numerous size control strategies operating at different cell cycle stages, but it is less clear how each contributes to the overall size control program. It is also unknown how robust each control system is to large perturbations in cell volume. Since unperturbed cells proliferating in nutrient-rich environments typically grow less than twofold from birth to division, addressing the robustness of size control mechanisms requires a means of acutely perturbing growth to dramatically alter this size distribution. Here, we employed an optogenetic system to reversibly block cell polarization and division in budding yeast. While blocked, cells continued to grow isotropically, increasing in volume by up to 30-fold over unperturbed cells. Upon release, these ‘giant’ yeast began to proliferate and the population returned to its initial volume distribution. Size control in unperturbed yeast was consistent with an ‘adder’ mechanism, as previously described, where cells add a constant volume between division events. In contrast, this ‘adder’ failed to explain our observations in giant yeast and volume regulation was instead better described by an invariant bud growth ‘timer’. Our results indicate that yeast size control arises from distinct mechanisms that employ both size sensors and timers to ensure a uniform volume distribution.