A novel role of the stress-activated protein kinase network p38/HOG in coupling growth to division in Candida albicans

The basis for commitment to cell division in late G1 phase, called Start in yeast and the Restriction Point in metazoans, is a critical but still poorly understood aspect of eukaryotic cell proliferation. All eukaryotic cells must grow to a critical cell size before commitment to division occurs. This size threshold couples cell growth to division and thereby establishes long-term size homeostasis. Here, to address the problem of cell size control across different species, we performed the first quantitative survey of the size phenome in the pathogenic yeast Candida albicans by focusing on mutants of transcriptional regulators and kinases. We investigate one of the divergent size regulatory pathways in C. albicans, the p38/HOG MAPK module, to uncover a novel stress-independent function for the HOG module in size control. We show that Hog1 inhibits G1/S transcription to delay the G1/S transition and that Hog1 also controls ribosome biogenesis gene expression. These results suggest that Hog1 represents a critical and previously unsuspected nexus between the growth and division machineries. Our study thus delineates the overall genetic basis for size control in C. albicans and identifies, to our knowledge, the first specific conduit that couples cell growth to cell division. To investigate the role of Hog1 in Start control in C. albicans, we performed genome-wide transcriptional profiling by microarray. G1-cells of both hog1 mutant and the parental WT strain were collected by centrifugal elutriation, grown for 10 min at 30°C in fresh YPD medium and their transcriptomes were characterized. Using the same experimental setup, we performed genome wide occupancy experiment (YPD, 30°C) with Hog1-TAP to determine its binding sites.