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Integrating phenotypic and expression profiles to map arsenic-response networks.
Astrid C Haugen1, Ryan Kelley, Jennifer B Collins
1Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA. Haugen@niehs.nih.gov <Haugen@niehs.nih.gov>
Genome Biology
|December 4, 2004
Summary
Arsenic exposure impacts yeast cells by altering metabolic networks and protein turnover. This study reveals how yeast adapts to arsenic stress through specific gene regulation and metabolic pathway shifts.
Area of Science:
- Biochemistry
- Cellular Biology
- Toxicology
Background:
- Arsenic is a widespread toxic metalloid and non-mutagenic carcinogen.
- Understanding its cellular impact is crucial for public health.
- Saccharomyces cerevisiae serves as a model organism to study arsenic's effects.
Purpose of the Study:
- To investigate the cellular impact of arsenic in yeast.
- To map gene expression and sensitivity phenotypes to cellular networks.
- To elucidate the mechanisms of arsenic adaptation and toxicity.
Main Methods:
- Global gene expression profiling.
- Sensitivity phenotyping.
- Network analysis integrating metabolic and protein-protein/DNA interaction networks.
Main Results:
- Regulatory network analysis identified key proteins (Fhl1, Msn2, Msn4, Yap1, Cad1, Pre1, Hsf1, Met31) central to arsenic response.
- Phenotypic profiling highlighted the shikimate and serine/threonine/glutamate biosynthesis pathways.
- Transcriptional profiling of deletion strains confirmed Yap1, Arr1, and Rpn4 as key mediators of arsenic adaptation.
Conclusions:
- Arsenic likely channels sulfur into glutathione for detoxification.
- It causes indirect oxidative stress by depleting glutathione.
- Arsenic alters protein turnover through protein arsenation.
- Phenotypically sensitive pathways are upstream of differentially expressed ones, indicating distinct yet related cellular responses.