Analysis of Saccharomyces cerevisiae Null Allele Strains Identifies a Larger Role for DNA Damage Versus Oxidative Stress Pathways in Growth Inhibition by Selenium
Molecular Nutrition and Food Research
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 ∼︁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 ∼︁28–36% in SeMet. Interestingly both compounds reduced growth in ∼︁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.
Seitomer, Eden; Balar, Bharvi; He, Dongming; Copeland, Paul R.; and Kinzy, Terri Goss, "Analysis of Saccharomyces cerevisiae Null Allele Strains Identifies a Larger Role for DNA Damage Versus Oxidative Stress Pathways in Growth Inhibition by Selenium" (2008). Faculty Publications – Biological Sciences. 84.
This article was originally published as Seitomer, E., Balar, B., He, D., Copeland, P.R., and Kinzy, T.G. (2008) Analysis of Saccharomyces cerevisiae Null Allele Strains Identifies a Larger Role For DNA Damage Verses Oxidative Stress Pathways in Reduced Growth in Selenium. Molecular Nutrition and Food Research 52:1305-15 PMC2650619.