A systematic cell size screen uncovers coupling of growth to division by the p38/HOG network in Candida albicans

Abstract

Cell size is a complex trait that responds to developmental and environmental cues. Quantitative analysis of the size phenome in the pathogenic yeast Candida albicans uncovered 195 genes that markedly altered cell size, few of which overlapped with known size genes in other yeast species. A potent size regulator specific to C. albicans was the conserved p38/HOG MAPK module that mediates the osmotic stress response. Basal HOG activity inhibited the SBF G1/S transcription factor complex in a stress-independent fashion to delay the G1/S transition. The HOG network also governed ribosome biogenesis through the master transcriptional regulator Sfp1. Hog1 bound to the promoters and cognate transcription factors for both the G1/S and ribosome biogenesis regulons and thereby directly linked cell growth and division. These results illuminate the evolutionary plasticity of size control and identify the HOG module as a nexus of cell cycle and growth regulation.