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Title: A genome-wide screen identifies yeast genes required for tolerance to technical toxaphene, an organochlorinated pesticide mixture.

Authors: Gaytán, Brandon D; Loguinov, Alex V; Peñate, Xenia; Lerot, Jan-Michael; Chávez, Sebastián; Denslow, Nancy D; Vulpe, Chris D

Published In PLoS One, (2013)

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.

PubMed ID: 24260565 Exiting the NIEHS site

MeSH Terms: Dose-Response Relationship, Drug; Drug Synergism; Gene Deletion; Gene Expression Regulation, Fungal*; Gene Regulatory Networks; Genome, Fungal*; Humans; Insecticides/pharmacology*; Metabolic Networks and Pathways; Molecular Sequence Annotation; Mycophenolic Acid/pharmacology; Saccharomyces cerevisiae Proteins/genetics*; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/drug effects*; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Sequence Homology, Amino Acid; Toxaphene/pharmacology*; Transcription Elongation, Genetic/drug effects

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