Superfund Research Program
Genetic Susceptibility to Superfund Chemicals
Project Leader: Martyn T. Smith
Co-Investigator: Luoping Zhang
Grant Number: P42ES004705
Funding Period: 2006-2017
Project-Specific Links
Title: Functional profiling in yeast with the benzene metabolites hydroquinone, catechol and 1,2,4-benzenetriol
Accession Number: GSE45116
Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45116
Repository: Gene Expression Omnibus (GEO)
Data Type(s): Gene Expression
Organism(s): Saccharomyces cerevisiae
Summary: 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.
Publication(s) associated with this dataset:- North M, Tandon VJ, Thomas R, Loguinov AV, Gerlovina I, Hubbard AE, Zhang L, Smith MT, Vulpe CD. 2011. Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. PLoS One 6(8):e24205. doi:10.1371/journal.pone.0024205 PMID:21912624 PMCID:PMC3166172