Oxidative Stress Responses and Nutrient Starvation in MCHM Treated Saccharomyces cerevisiae
| Autor: | Jennifer E. G. Gallagher, Zachary N. Sherman, Michael C. Ayers |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Saccharomyces cerevisiae Proteins
DNA damage Saccharomyces cerevisiae Investigations QH426-470 010501 environmental sciences medicine.disease_cause 01 natural sciences environmental stress response Transcriptome 03 medical and health sciences chemistry.chemical_compound nutrient starvation Genetics medicine Aromatic amino acids saccharomyces cerevisiae tryptophan Molecular Biology Gene Genetics (clinical) 030304 developmental biology 0105 earth and related environmental sciences reactive oxygen species chemistry.chemical_classification mchm 0303 health sciences biology Methanol aromatic amino acids Translation (biology) Nutrients biology.organism_classification Amino acid Cell biology Oxidative Stress chemistry genetic screen Oxidative stress |
| Zdroj: | G3: Genes, Genomes, Genetics, Vol 10, Iss 12, Pp 4665-4678 (2020) G3: Genes|Genomes|Genetics |
| ISSN: | 2160-1836 |
| Popis: | In 2014, the coal cleaning chemical 4-methylcyclohexane methanol (MCHM) spilled into the water supply for 300,000 West Virginians. Initial toxicology tests showed relatively mild results, but the underlying effects on cellular biology were underexplored. Treated wildtype yeast cells grew poorly, but there was only a small decrease in cell viability. Cell cycle analysis revealed an absence of cells in S phase within thirty minutes of treatment. Cells accumulated in G1 over a six-hour time course, indicating arrest instead of death. A genetic screen of the haploid knockout collection revealed 329 high confidence genes required for optimal growth in MCHM. These genes encode three major cell processes: mitochondrial gene expression/translation, the vacuolar ATPase, and aromatic amino acid biosynthesis. The transcriptome showed an upregulation of pleiotropic drug response genes and amino acid biosynthetic genes and downregulation in ribosome biosynthesis. Analysis of these datasets pointed to environmental stress response activation upon treatment. Overlap in datasets included the aromatic amino acid genes ARO1, ARO3, and four of the five TRP genes. This implicated nutrient deprivation as the signal for stress response. Excess supplementation of nutrients and amino acids did not improve growth on MCHM, so the source of nutrient deprivation signal is still unclear. Reactive oxygen species and DNA damage were directly detected with MCHM treatment, but timepoints showed these accumulated slower than cells arrested. We propose that wildtype cells arrest from nutrient deprivation and survive, accumulating oxidative damage through the implementation of robust environmental stress responses. |
| Databáze: | OpenAIRE |
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