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- Title
Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast.
- Authors
North, Matthew; Tandon, Vickram J; Thomas, Reuben; Loguinov, Alex; Gerlovina, Inna; Hubbard, Alan E; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D
- 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.
- Publication
PloS one, 2011, Vol 6, Issue 8, pe24205
- ISSN
1932-6203
- Publication type
Journal Article
- DOI
10.1371/journal.pone.0024205