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Updated: Jun 21, 2026
Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae
Published on: April 5, 2015
A genome-wide screen in Saccharomyces cerevisiae reveals pathways affected by arsenic toxicity
Xue Zhou1, Adriana Arita, Thomas P Ellen
1Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Abstract:
We have used Saccharomyces cerevisiae to identify toxicologically important proteins and pathways involved in arsenic-induced toxicity and carcinogenicity in humans. We performed a systemic screen of the complete set of 4733 haploid S. cerevisiae single-gene-deletion mutants to identify those that have decreased or increased growth, relative to wild type, after exposure to sodium arsenite (NaAsO(2)). IC(50) values for all mutants were determined to further validate our results. Ultimately we identified 248 mutants sensitive to arsenite and 5 mutants resistant to arsenite exposure. We analyzed the proteins corresponding to arsenite-sensitive mutants and determined that they belonged to functional categories that include protein binding, phosphate metabolism, vacuolar/lysosomal transport, protein targeting, sorting, and translocation, cell growth/morphogenesis, cell polarity and filament formation. Furthermore, these data were mapped onto a protein interactome to identify arsenite-toxicity-modulating networks. These networks are associated with the cytoskeleton, ubiquitination, histone acetylation and the MAPK signaling pathway. Our studies have potential implications for understanding toxicity and carcinogenesis in arsenic-induced human conditions, such as cancer and aging.
Insights
Researchers screened yeast mutants to find proteins and pathways involved in arsenic toxicity. This study identified key cellular processes and networks affected by arsenic, offering insights into arsenic-induced human health risks like cancer.
Area of Science:
- Toxicology
- Molecular Biology
- Genetics
Background:
- Arsenic exposure is linked to human toxicity and carcinogenicity.
- Understanding the molecular mechanisms of arsenic toxicity is crucial for human health.
- Saccharomyces cerevisiae serves as a model organism for studying fundamental biological processes.
Purpose of the Study:
- To identify toxicologically important proteins and pathways in arsenic-induced toxicity and carcinogenicity using yeast.
- To screen a comprehensive set of yeast gene-deletion mutants for altered growth in the presence of sodium arsenite.
- To map identified genes onto a protein interactome to uncover arsenic-toxicity-modulating networks.
Main Methods:
- Systematic screening of 4733 haploid Saccharomyces cerevisiae single-gene-deletion mutants.
- Exposure to sodium arsenite (NaAsO(2)) to assess growth inhibition or enhancement.
- Determination of IC(50) values for validation.
- Functional analysis of proteins corresponding to sensitive mutants.
- Mapping data onto a protein interactome.
Main Results:
- Identified 248 arsenite-sensitive and 5 arsenite-resistant mutants.
- Arsenite-sensitive proteins are involved in protein binding, phosphate metabolism, vacuolar transport, protein targeting, cell growth, polarity, and filament formation.
- Arsenite-toxicity-modulating networks are associated with the cytoskeleton, ubiquitination, histone acetylation, and MAPK signaling pathways.
Conclusions:
- This study elucidates key cellular components and networks perturbed by arsenic exposure in a model organism.
- The findings provide a foundation for understanding arsenic-induced toxicity and carcinogenicity in humans.
- Implications for human conditions such as cancer and aging linked to arsenic exposure.
