Cells slow down cell cycle progression in order to adapt to unfavorable stress conditions. Yeast respond to osmotic stress by triggering G1 and G2 checkpoint delays that is dependent on the mitogen-activated protein kinase (MAPK) Hog1. The high osmolarity glycerol (HOG) pathway is also activated by arsenite and the hog1Delta mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1Delta cells. Yeast cell cycle regulation in response to arsenite and the role of Hog1 in this process have not yet been analyzed. Here, we found that long-term exposure to arsenite led to transient G1 and G2 delays in wild type cells whereas cells that lack the HOG1 gene or are defective in Hog1 kinase activity displayed persistent G1 cell cycle arrest. Elevated levels of intracellular arsenite and 'cross talk' between the HOG and pheromone response pathways, observed in arsenite-treated hog1Delta cells, prolonged the G1 delay but did not cause a persistent G1 arrest. In contrast, deletion of the SIC1 gene encoding a cyclin-dependent kinase inhibitor fully suppressed the observed block of G1 exit in hog1Delta. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1Delta cells. Interestingly, Sic1-dependent persistent G1 arrest was also observed in hog1Delta cells during hyper-osmotic stress. Taken together, our data point to an important role of the Hog1 kinase in adaptation to stress-induced G1 cell cycle arrest.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|