Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast.
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...
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doaj-17ed7b67440b41d69789b04b94870c9d2020-11-25T01:38:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2420510.1371/journal.pone.0024205Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast.Matthew NorthVickram J TandonReuben ThomasAlex LoguinovInna GerlovinaAlan E HubbardLuoping ZhangMartyn T SmithChris D VulpeBenzene 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.http://europepmc.org/articles/PMC3166172?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew North Vickram J Tandon Reuben Thomas Alex Loguinov Inna Gerlovina Alan E Hubbard Luoping Zhang Martyn T Smith Chris D Vulpe |
spellingShingle |
Matthew North Vickram J Tandon Reuben Thomas Alex Loguinov Inna Gerlovina Alan E Hubbard Luoping Zhang Martyn T Smith Chris D Vulpe Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. PLoS ONE |
author_facet |
Matthew North Vickram J Tandon Reuben Thomas Alex Loguinov Inna Gerlovina Alan E Hubbard Luoping Zhang Martyn T Smith Chris D Vulpe |
author_sort |
Matthew North |
title |
Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. |
title_short |
Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. |
title_full |
Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. |
title_fullStr |
Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. |
title_full_unstemmed |
Genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. |
title_sort |
genome-wide functional profiling reveals genes required for tolerance to benzene metabolites in yeast. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3166172?pdf=render |
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