title: Yap1: a DNA damage responder in Saccharomyces cerevisiae.
abstract: Activation of signaling pathways in response to genotoxic stress is crucial for cells to properly repair DNA damage. In response to DNA damage, intracellular levels of reactive oxygen species increase. One important function of such a response could be to initiate signal transduction processes. We have employed the model eukaryote Saccharomyces cerevisiae to delineate DNA damage sensing mechanisms. We report a novel, unanticipated role for the transcription factor Yap1 as a DNA damage responder, providing direct evidence that reactive oxygen species are an important component of the DNA damage signaling process. Our findings reveal an epistatic link between Yap1 and the DNA base excision repair pathway. Corruption of the Yap1-mediated DNA damage response influences cell survival and genomic stability in response to exposure to genotoxic agents.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, 30322, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Rowe
authors.forename: Natalya
authors.initials: N
authors.lastname: Degtyareva
authors.forename: Paul W
authors.initials: PW
authors.lastname: Doetsch
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D002869:Chromosome Aberrations; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004843:Epistasis, Genetic; D042822:Genomic Instability; D006861:Hydrogen Peroxide / Q000633:toxicity; D008741:Methyl Methanesulfonate / Q000633:toxicity; D050296:Microbial Viability; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009153:Mutagens; D016877:Oxidants; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D013481:Superoxides; D008741:Methyl Methanesulfonate; D006861:Hydrogen Peroxide