Johnson AJ~Wu MJ, 2015

Pubmed ID 26688044
Title Molecular insight into arsenic toxicity via the genome-wide deletion mutant screening of Saccharomyces cerevisiae.
Authors Adam J Johnson, Filip Veljanoski, Patrick J O'Doherty, Mohammad S Zaman, Gayani Petersingham, Trevor D Bailey, Gerald Münch, Cindy Kersaitis, Ming J Wu
Abstract Arsenic is omnipresent in soil, air, food and water. Chronic exposure to arsenic is a serious problem to human health. In-depth understanding of this metalloid's toxicity is a fundamental step towards development of arsenic-free foods and measures for bioremediation. By screening the complete set of gene deletion mutants (4873) of Saccharomyces cerevisiae, this study uncovered 75 sensitive and 39 resistant mutants against arsenite [As(III)]. Functional analysis of the corresponding genes revealed the molecular details for its uptake, toxicity and detoxification. On the basis of the hypersensitivity of yap3Δ, the transcription factor, Yap3p, is for the first time linked to the cell's detoxification against As(III). Apart from confirming the previously described role of the mitogen-activated protein kinase (MAPK) Hog1 pathway in combating arsenic toxicity, the results show that the regulatory subunits (Ckb1p and Ckb2p) of protein kinase CK2 are also involved in the process, suggesting possible crosstalk between the two key protein kinases. The sensitivity to As(III) conferred by deletion of the genes involved in protein degradation and chromatin remodelling demonstrates protein damage is the key mode of toxicity for the metalloid. Furthermore, the resistant phenotype of fps1Δ, snf3Δ and pho81Δ against As(III) links arsenic uptake with the corresponding plasma membrane-bound transporters-aquaglyceroporin (Fps1p), hexose (Snf3p) and phosphate transporters. The molecular details obtained in this screen for As(III) uptake, detoxification and toxicity provide the basis for future investigations into arsenic-related problems in the environment, agriculture and human health.
Citation Metallomics 2016; 8:228-35
Notes Arsenic toxicity screening of the full set of 4873 homozygous deletion mutants for non-essential genes.

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Johnson AJ~Wu MJ, 2015 growth (culture turbidity) sodium arsenite [0.2 mM] hom 4,870 Quantitative
Johnson AJ~Wu MJ, 2015 growth (culture turbidity) sodium arsenite [0.4 mM] hom 4,870 Quantitative

Curation history

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