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University of California-Berkeley: Dataset Details, ID=GSE17950

Superfund Research Program

Toxic Substances in the Environment

Center Director: Martyn T. Smith
Grant Number: P42ES004705
Funding Period: 1987-2027
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Title: Functional profiling in yeast with arsenite and monomethylarsonous acid

Accession Number: GSE17950

Link to Dataset:

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Organism(s): Saccharomyces cerevisiae

Summary: Arsenic is a human toxin and carcinogen commonly found as a contaminant in drinking water. Arsenite (AsIII) is the most toxic inorganic form, but recent evidence indicates that the metabolite monomethylarsonous acid (MMAIII) is even more toxic. We have used a chemical genomics approach to identify the genes that modulate the cellular toxicity of MMAIII and AsIII in the yeast Saccharomyces cerevisiae. Functional profiles provided evidence of the requirement of highly-conserved biological processes in the response against both arsenicals including tubulin folding, DNA double-strand break repair and chromatin modification. At the equitoxic doses of 150 µM MMAIII and 300 µM AsIII, genes related to glutathione were essential only for resistance to the former, suggesting a higher potency of MMAIII to disrupt glutathione metabolism than AsIII. Treatments with MMAIII induced an increase in glutathione levels, which correlated to the requirement of genes from the sulfur and methionine metabolic pathways. Many of the identified yeast genes have orthologs in humans that could potentially modulate arsenic toxicity in a similar manner as their yeast counterparts.

Publication(s) associated with this dataset:
  • Jo WJ, Loguinov AV, Wintz H, Chang M, Smith AH, Vulpe CD, Kalman DA, Zhang L, Smith MT. 2009. Comparative functional genomic analysis identifies distinct and overlapping sets of genes required for resistance to monomethylarsonous acid (MMAIII) and arsenite (AsIII) in yeast. Toxicol Sci 111(2):424-436. doi:10.1093/toxsci/kfp162 PMID:19635755 PMCID:PMC2742584
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