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A genome-wide screen of genes involved in cadmium tolerance in Schizosaccharomyces pombe

Academic Article
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Overview

authors

  • Kennedy, P. J.
  • Vashisht, A. A.
  • Hoe, K. L.
  • Kim, Dae Hee
  • Park, H. O.
  • Hayles, J.
  • Russell, Paul

publication date

  • November 2008

journal

  • Toxicological Sciences  Journal

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.

subject areas

  • Cadmium Compounds
  • Cell Proliferation
  • Environmental Pollutants
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Genome, Fungal
  • Genotype
  • Hydrogen Peroxide
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Osmotic Pressure
  • Oxidative Stress
  • Phenotype
  • Potassium Chloride
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Sulfates
  • Time Factors
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Research

keywords

  • Schizosaccharomyces pombe
  • cadmium
  • gene deletion
  • stress
  • sulfur
  • ubiquinone
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Identity

PubMed Central ID

  • PMC2563147

International Standard Serial Number (ISSN)

  • 1096-6080

Digital Object Identifier (DOI)

  • 10.1093/toxsci/kfn153

PubMed ID

  • 18684775
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Additional Document Info

start page

  • 124

end page

  • 139

volume

  • 106

issue

  • 1

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