Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae.
Journal article, 2009
BACKGROUND: Arsenic and cadmium are widely distributed in nature and pose serious threats to the environment and human health. Exposure to these nonessential toxic metals may result in a variety of human diseases including cancer. However, arsenic and cadmium toxicity targets and the cellular systems contributing to tolerance acquisition are not fully known. RESULTS: To gain insight into metal action and cellular tolerance mechanisms, we carried out genome-wide screening of the Saccharomyces cerevisiae haploid and homozygous diploid deletion mutant collections and scored for reduced growth in the presence of arsenite or cadmium. Processes found to be required for tolerance to both metals included sulphur and glutathione biosynthesis, environmental sensing, mRNA synthesis and transcription, and vacuolar/endosomal transport and sorting. We also identified metal-specific defence processes. Arsenite-specific defence functions were related to cell cycle regulation, lipid and fatty acid metabolism, mitochondrial biogenesis, and the cytoskeleton whereas cadmium-specific defence functions were mainly related to sugar/carbohydrate metabolism, and metal-ion homeostasis and transport. Molecular evidence indicated that the cytoskeleton is targeted by arsenite and that phosphorylation of the Snf1p kinase is required for cadmium tolerance. CONCLUSION: This study has pin-pointed core functions that protect cells from arsenite and cadmium toxicity. It also emphasizes the existence of both common and specific defence systems. Since many of the yeast genes that confer tolerance to these agents have homologues in humans, similar biological processes may act in yeast and humans to prevent metal toxicity and carcinogenesis.
Mutation
Protein-Serine-Threonine Kinases
Fungal
Arsenites
genetics
Saccharomyces cerevisiae
Cadmium
toxicity
metabolism
Genome
metabolism
Stress
metabolism
Cytoskeleton
genetics
Saccharomyces cerevisiae Proteins
Humans
Oxidative Stress
metabolism
Gene Expression Profiling
toxicity
Phosphorylation
Physiological
Haploidy
Author
Michael Thorsen
University of Gothenburg
Gabriel G Perrone
University of New South Wales (UNSW)
Erik Kristiansson
University of Gothenburg
Mathew Traini
University of New South Wales (UNSW)
Tian Ye
University of Gothenburg
Ian W Dawes
University of New South Wales (UNSW)
Olle Nerman
University of Gothenburg
Chalmers, Mathematical Sciences, Mathematical Statistics
Markus J. Tamás
University of Gothenburg
BMC Genomics
14712164 (eISSN)
Vol. 10 105- 105Subject Categories
Biochemistry and Molecular Biology
Genetics
DOI
10.1186/1471-2164-10-105
PubMed
19284616