To ensure their survival, cells arrest the cell division cycle when they are exposed to environmental stress. The duration of this arrest is dependent upon the time it takes a cell to adapt to a particular environment. How cells adjust the amount of time they remain arrested is not known. This study investigates the role of the phosphatase calcineurin in controlling cell cycle arrest duration in yeast. We show that calcineurin lengthens arrest by prolonging Hog1-dependent activation of the poorly characterized cyclin-dependent kinase inhibitor Cip1. Cip1 only impacts cell cycle arrest in response to stressors that robustly activate calcineurin, suggesting that Cip1 is a context-specific regulator that differentially adjusts the length of arrest depending on the particular stressor.
Cells exposed to environmental stress arrest the cell cycle until they have adapted to their new environment. Cells adjust the length of the arrest for each unique stressor, but how they do this is not known. Here, we investigate the role of the stress-activated phosphatase calcineurin (CN) in controlling cell cycle arrest in Saccharomyces cerevisiae. We find that CN controls arrest duration through activation of the G1 cyclin–dependent kinase inhibitor Cip1. Our results demonstrate that multiple stressors trigger a G1/S arrest through Hog1-dependent down-regulation of G1 cyclin transcription. When a stressor also activates CN, this arrest is lengthened as CN prolongs Hog1-dependent phosphorylation of Cip1. Cip1 plays no role in response to stressors that activate Hog1 but not CN. These findings illustrate how stress response pathways cooperate to tailor the stress response and suggest that Cip1 functions to prolong cell cycle arrest when a cell requires additional time for adaptation.