title: A genome-wide screen of genes involved in cadmium tolerance in Schizosaccharomyces pombe.
abstract: Cadmium is a worldwide environmental toxicant responsible for a range of human diseases including cancer. Cellular injury from cadmium is minimized by stress-responsive detoxification mechanisms. We explored the genetic requirements for cadmium tolerance by individually screening mutants from the fission yeast (Schizosaccharomyces pombe) haploid deletion collection for inhibited growth on agar growth media containing cadmium. Cadmium-sensitive mutants were further tested for sensitivity to oxidative stress (hydrogen peroxide) and osmotic stress (potassium chloride). Of 2649 mutants screened, 237 were sensitive to cadmium, of which 168 were cadmium specific. Most were previously unknown to be involved in cadmium tolerance. The 237 genes represent a number of pathways including sulfate assimilation, phytochelatin synthesis and transport, ubiquinone (Coenzyme Q10) biosynthesis, stress signaling, cell wall biosynthesis and cell morphology, gene expression and chromatin remodeling, vacuole function, and intracellular transport of macromolecules. The ubiquinone biosynthesis mutants are acutely sensitive to cadmium but only mildly sensitive to hydrogen peroxide, indicating that Coenzyme Q10 plays a larger role in cadmium tolerance than just as an antioxidant. These and several other mutants turn yellow when exposed to cadmium, suggesting cadmium sulfide accumulation. This phenotype can potentially be used as a biomarker for cadmium. There is remarkably little overlap with a comparable screen of the Saccharomyces cerevisiae haploid deletion collection, indicating that the two distantly related yeasts utilize significantly different strategies for coping with cadmium stress. These strategies and their relation to cadmium detoxification in humans are discussed.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Kennedy
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.forename: Kwang-Lae
authors.initials: KL
authors.lastname: Hoe
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: Han-Oh
authors.initials: HO
authors.lastname: Park
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hayles
authors.forename: Paul
authors.initials: P
authors.lastname: Russell
mesh_terms: D019187:Cadmium Compounds / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D020869:Gene Expression Profiling / Q000379:methods; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D016681:Genome, Fungal; D005838:Genotype; D006861:Hydrogen Peroxide / Q000633:toxicity; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D009997:Osmotic Pressure / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010641:Phenotype; D011189:Potassium Chloride / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D013431:Sulfates / Q000633:toxicity*; D013997:Time Factors
chemical_list: D019187:Cadmium Compounds; D004785:Environmental Pollutants; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D013431:Sulfates; D011189:Potassium Chloride; C037123:cadmium sulfate; D006861:Hydrogen Peroxide