ABSTRACT: BACKGROUND: The cellular mechanisms underlying metal toxicity and detoxification are extremely variegated and incompletely understood. Genomic phenotyping was used to assess the role of all non-essential S. cerevisiae proteins in modulating cell viability after exposure to cadmium, nickel and other metals. RESULTS: A number of novel genes and pathways affecting multimetal as well as metal-specific tolerance were discovered. Although the vacuole emerged as a major hot-spot for metal detoxification, we also identified a number of pathways playing a more general, less direct role in promoting cell survival under stress conditions (e.g., mRNA decay, nucleo-cytoplasmic transport and iron acquisition) as well as proteins more proximally related to metal damage prevention or repair. Most prominent among the latter are various nutrient transporters previously not associated with metal toxicity. A strikingly differential effect was observed for a large set of deletions, the majority of which centred on the ESCRT and retromer complexes, that by affecting transporter downregulation and intracellular protein traffic cause cadmium sensitivity, but nickel resistance. CONCLUSIONS: The data show that a previously underestimated variety of pathways are involved in cadmium and nickel tolerance in eukaryotic cells. As revealed by comparison with five additional metals, there is a good correlation between the chemical properties and the cellular toxicity signatures of different metals. However, many conserved pathways centred on membrane transporters and protein traffic affect cell viability with a surprisingly high degree of metal specificity.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|