Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 21912624.
- Also identified by DOI 10.1371/journal.pone.0024205 and PMC identifier 3166172.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Benzene is a ubiquitous environmental contaminant and is widely used in industry. Exposure to benzene causes a number of serious health problems, including blood disorders and leukemia. Benzene undergoes complex metabolism in humans, making mechanistic determination of benzene toxicity difficult. We used a functional genomics approach to identify the genes that modulate the cellular toxicity of three of the phenolic metabolites of benzene, hydroquinone (HQ), catechol (CAT) and 1,2,4-benzenetriol (BT), in the model eukaryote Saccharomyces cerevisiae. Benzene metabolites generate oxidative and cytoskeletal stress, and tolerance requires correct regulation of iron homeostasis and the vacuolar ATPase. We have identified a conserved bZIP transcription factor, Yap3p, as important for a HQ-specific response pathway, as well as two genes that encode putative NAD(P)H:quinone oxidoreductases, PST2 and YCP4. Many of the yeast genes identified have human orthologs that may modulate human benzene toxicity in a similar manner and could play a role in benzene exposure-related disease.
Medical subject headings
- Active Transport, Cell Nucleus
- Active Transport, Cell Nucleus/drug effects
- Amino Acid Sequence
- Animals
- Benzene
- Benzene/metabolism
- Cell Nucleus
- Cell Nucleus/drug effects
- Cell Nucleus/metabolism
- Cluster Analysis
- Cytoskeleton
- Cytoskeleton/drug effects
- Cytoskeleton/metabolism
- Dose-Response Relationship, Drug
- Endoplasmic Reticulum Stress
- Endoplasmic Reticulum Stress/drug effects
- Fungal Proteins
- Fungal Proteins/chemistry
- Fungal Proteins/genetics
- Fungal Proteins/metabolism
- Genes, Fungal
- Genes, Fungal/genetics
- Genomics
- Homeostasis
- Homeostasis/drug effects
- Humans
- Iron
- Iron/metabolism
- Membrane Lipids
- Membrane Lipids/metabolism
- Molecular Sequence Data
- NAD(P)H Dehydrogenase (Quinone)
- NAD(P)H Dehydrogenase (Quinone)/chemistry
- NAD(P)H Dehydrogenase (Quinone)/genetics
- NAD(P)H Dehydrogenase (Quinone)/metabolism
- NADP
- NADP/metabolism
- Phenols
- Phenols/metabolism
- Phenols/toxicity
- Saccharomyces cerevisiae
- Saccharomyces cerevisiae/cytology
- Saccharomyces cerevisiae/drug effects
- Saccharomyces cerevisiae/genetics
- Saccharomyces cerevisiae/growth & development
- Species Specificity
- Time Factors
- Vacuolar Proton-Translocating ATPases
- Vacuolar Proton-Translocating ATPases/genetics
- Vacuolar Proton-Translocating ATPases/metabolism
- Vacuoles
- Vacuoles/drug effects
- Vacuoles/metabolism