title: Revelation of molecular basis for chromium toxicity by phenotypes of Saccharomyces cerevisiae gene deletion mutants.
abstract: Chromium toxicity is increasingly relevant to living organisms such as humans, due to the environmental contamination of chromium and the application of stainless steel-based medical devices like hip prostheses. Despite the investigations in past years, the molecular details for chromium toxicity remain to be delineated. In this study, we seek to gain insights into the molecular aspects of chromium toxicity by screening a genome-wide deletion set of individual genes in Saccharomyces cerevisiae against hexavalent chromium [Cr(vi)] using chromium trioxide. From the primary data collected in this study, two lists of deletion mutants in response to Cr(vi) exposure were obtained, one for the sensitive phenotype and the other for the resistant phenotype. The functional analysis of the genes corresponding to the sensitive mutants reveals the key features of Cr(vi) toxicity, which include genotoxicity, protein damage, disruption of energy and sulfur metabolisms. DNA repair, ubiquitination-mediated protein degradation, iron homeostasis and growth attenuation are the intrinsic facets of the cell's detoxification mechanisms. Protein kinase CK2 is, for the first time, found to be involved in regulating chromium toxicity by reducing the uptake of Cr(vi). Taken together, the findings provide meaningful details into the basic understanding of chromium toxicity in terms of its uptake, modes of action, cellular detoxification and molecular regulatory mechanisms.
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Johnson
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
authors.forename: Filip
authors.initials: F
authors.lastname: Veljanoski
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: O'Doherty
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Zaman
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
authors.forename: Gayani
authors.initials: G
authors.lastname: Petersingham
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
authors.forename: Trevor D
authors.initials: TD
authors.lastname: Bailey
authors.affiliation: Department of Pharmacology, School of Medicine and Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia.
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au.
authors.forename: Cindy
authors.initials: C
authors.lastname: Kersaitis
authors.affiliation: School of Science and Health, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia. m.wu@westernsydney.edu.au and Department of Pharmacology, School of Medicine and Molecular Medicine Research Group, Western Sydney University, Locked Bag 1797, Penrith, NSW 2751, Australia.
authors.forename: Ming J
authors.initials: MJ
authors.lastname: Wu
mesh_terms: D002857:Chromium / Q000633:toxicity*; D004249:DNA Damage; D017353:Gene Deletion; D005800:Genes, Fungal; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics
chemical_list: D002857:Chromium; C074702:chromium hexavalent ion