title: Analysis of Saccharomyces cerevisiae null allele strains identifies a larger role for DNA damage versus oxidative stress pathways in growth inhibition by selenium.
abstract: Selenium toxicity is a growing environmental concern due to widespread availability of high-dose selenium supplements and the development of high-selenium agricultural drainage basins. To begin to analyze the effects of selenium toxicity at the genetic level, we have systematically determined which genes are involved in responding to high environmental selenium using a collection of viable haploid null allele strains of Saccharomyces cerevisiae representing three major stress pathways: the RAD9-dependent DNA repair pathway, the RAD6/RAD18 DNA damage tolerance pathway, and the oxidative stress pathway. A total of 53 null allele strains were tested for growth defects in the presence of a range of sodium selenite and selenomethionine (SeMet) concentrations. Our results show that approximately 64-72% of the strains lacking RAD9-dependent DNA repair or RAD6/RAD18 DNA damage tolerance pathway genes show reduced growth in sodium selenite versus approximately 28-36% in SeMet. Interestingly both compounds reduced growth in approximately 21-25% of the strains lacking oxidative stress genes. These data suggest that both selenite and SeMet are likely inducing DNA damage by generating reactive species. The anticipated effects of loss of components of the oxidative stress pathway were not observed, likely due to apparent redundancies in these gene products that may keep the damaging effects in check.
authors.affiliation: Department of Molecular Genetics, Microbiology and Immunology, UMDNJ Robert Wood Johnson Medical School, NJ 08854-5635, USA.
authors.forename: Eden
authors.initials: E
authors.lastname: Seitomer
authors.forename: Bharvi
authors.initials: B
authors.lastname: Balar
authors.forename: Dongming
authors.initials: D
authors.lastname: He
authors.forename: Paul R
authors.initials: PR
authors.lastname: Copeland
authors.forename: Terri Goss
authors.initials: TG
authors.lastname: Kinzy
mesh_terms: D002455:Cell Division / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004271:DNA, Fungal / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011836:Radiation Tolerance / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics* / Q000528:radiation effects; D012643:Selenium / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D004271:DNA, Fungal; D012643:Selenium; D018038:Sodium Selenite