The Hog1 MAP kinase pathway and the Mec1 DNA damage checkpoint pathway independently control the cellular responses to hydrogen peroxide.
The DNA damage checkpoint pathway and the MAP kinase pathway respond to various forms of environmental as well as endogenous stresses through signal transduction mechanisms involving protein kinases. Both pathways are intertwined in mammalian cells, but potential crosstalk between these two pathways in budding yeast has not been examined yet. We show that the Rad53 checkpoint kinase and the Hog1 MAP kinase of Saccharomyces cerevisiae become phosphorylated upon exposure to hydrogen peroxide, indicative of activation of the DNA damage checkpoint and MAP kinase pathways in response to oxidative stress. Rad53 kinase is equally activated in wild type and in hog1-Delta cells. Likewise, the activation of Hog1 MAP kinase is not dependent on Mec1 kinase, the central checkpoint kinase in budding yeast. Mutants in either pathway are sensitive to hydrogen peroxide and the double mutants exhibit a near perfectly additive phenotype. These data demonstrate that the DNA damage checkpoint pathway and the MAP kinase pathway respond to oxidative stress independently of each other and suggest that these two stress signaling pathways are activated by different types of insults induced by hydrogen peroxide.
Haghnazari
Edwin
E
Division of Biological Sciences, Section of Microbiology and Section of Molecular and Cellular Biology and Center for Genetics and Development, University of California, Davis, CA 95616-8665, USA.
Heyer
Wolf-Dietrich
WD
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002470:Cell Survival; D064447:Checkpoint Kinase 2; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006861:Hydrogen Peroxide / Q000633:toxicity*; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D009154:Mutation; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C067022:RAD53 protein, S cerevisiae