title: A genome-wide screen identifies yeast genes required for tolerance to technical toxaphene, an organochlorinated pesticide mixture.
abstract: Exposure to toxaphene, an environmentally persistent mixture of chlorinated terpenes previously utilized as an insecticide, has been associated with various cancers and diseases such as amyotrophic lateral sclerosis. Nevertheless, the cellular and molecular mechanisms responsible for these toxic effects have not been established. In this study, we used a functional approach in the model eukaryote Saccharomyces cerevisiae to demonstrate that toxaphene affects yeast mutants defective in (1) processes associated with transcription elongation and (2) nutrient utilization. Synergistic growth defects are observed upon exposure to both toxaphene and the known transcription elongation inhibitor mycophenolic acid (MPA). However, unlike MPA, toxaphene does not deplete nucleotides and additionally has no detectable effect on transcription elongation. Many of the yeast genes identified in this study have human homologs, warranting further investigations into the potentially conserved mechanisms of toxaphene toxicity.
authors.affiliation: Department of Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, California, United States of America.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Gaytán
authors.forename: Alex V
authors.initials: AV
authors.lastname: Loguinov
authors.forename: Xenia
authors.initials: X
authors.lastname: Peñate
authors.forename: Jan-Michael
authors.initials: JM
authors.lastname: Lerot
authors.forename: Sebastián
authors.initials: S
authors.lastname: Chávez
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Denslow
authors.forename: Chris D
authors.initials: CD
authors.lastname: Vulpe
mesh_terms: D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D016681:Genome, Fungal; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D053858:Metabolic Networks and Pathways; D058977:Molecular Sequence Annotation; D009173:Mycophenolic Acid / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014112:Toxaphene / Q000494:pharmacology*; D061805:Transcription Elongation, Genetic / Q000187:drug effects
chemical_list: D007306:Insecticides; D029701:Saccharomyces cerevisiae Proteins; D014112:Toxaphene; D009173:Mycophenolic Acid