Systematic identification of cell size regulators in budding yeast

Abstract

Cell size is determined by a complex interplay between growth and division, involving multiple cellular pathways. To identify systematically processes affecting size control in G1 in budding yeast, we imaged and analyzed the cell cycle of millions of individual cells representing 591 mutants implicated in size control. Quantitative metric distinguished mutants affecting the mechanism of size control from the majority of mutants that have a perturbed size due to indirect effects modulating cell growth. Overall, we identified 17 negative and dozens positive size control regulators, with the negative regulators forming a small network centered on elements of mitotic exit network. Some elements of the translation machinery affected size control with a notable distinction between the deletions of parts of small and large ribosomal subunit: parts of small ribosomal subunit tended to regulate size control, while parts of the large subunit affected cell growth. Analysis of small cells revealed additional size control mechanism that functions in G2/M, complementing the primary size control in G1. Our study provides new insights about size control mechanisms in budding yeast. image New regulators of cell size are identified using a mutant screen based on high‐throughput time‐lapse microscopy. A quantitative framework distinguishes direct regulators of size control from mutants whose size is altered due to reduced growth rate. High‐throughput time‐lapse microscopy identified 17 negative and dozens positive regulators of cell size at START. Negative regulators form a small genetic network centered around the mitotic exit network, suggesting that G1 length depends on processes occurring prior to cell separation. The small ribosomal subunit affects size control, while the large subunit influences cell growth only, suggesting a role for translation initiation in size control. A backup mode of size control that functions in the budded phase is suggested.