Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae.
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.


CONCLUSIONS
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.
Thorsen
Michael
M
Department of Cell and Molecular Biology/Microbiology, University of Gothenburg, S-405 30 Gothenburg, Sweden. mthorsen@bio.ku.dk
Perrone
Gabriel G
GG
Kristiansson
Erik
E
Traini
Mathew
M
Ye
Tian
T
Dawes
Ian W
IW
Nerman
Olle
O
Tamás
Markus J
MJ
D018053:Arsenites / Q000633:toxicity*; D002104:Cadmium / Q000633:toxicity*; D003599:Cytoskeleton / Q000378:metabolism; D020869:Gene Expression Profiling; D016681:Genome, Fungal; D006238:Haploidy; D006801:Humans; D009154:Mutation; D018384:Oxidative Stress; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
D018053:Arsenites; D029701:Saccharomyces cerevisiae Proteins; D002104:Cadmium; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; C015001:arsenite