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Eukaryotic Cell doi:10.1128/EC.00038-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The MAPK Hog1 mediates adaptation to G₁ checkpoint arrest during arsenite and hyper-osmotic stress

Institute of Genetics and Microbiology, University of Wroclaw, 51-148 Wroclaw, Poland; Department of Cell and Molecular Biology/Microbiology, University of Gothenburg, S-405 30 Gothenburg, Sweden

^* To whom correspondence should be addressed. Email: wysocki{at}microb.uni.wroc.pl.

	Abstract

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 hog1 mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1 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 hog1 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 hog1. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1 cells. Interestingly, Sic1-dependent persistent G₁ arrest was also observed in hog1 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.