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Yeast mutants as a model system for identification of determinants of chemosensitivity
P Perego1, G S Jimenez, L Gatti
1Istituto Nazionale Tumori, Milan, Italy. perego@istitutotumori.mi.it
Abstract:
The fission yeast Schizosaccharomyces pombe and the budding yeast Saccharomyces cerevisiae have become valuable tools for the study of basic cellular functions of eukaryotic cells, including DNA repair mechanisms and cell cycle control. Since the major signaling pathways and cellular processes involved in cellular response to cytotoxic agents are conserved between yeasts and mammalian cells, these simple eukaryotic systems could be excellent models for the identification of molecular/cellular mechanisms of sensitivity to antitumor drugs. We describe relevant biological features of yeast cells and potential applications derived by their genetic manipulation. In particular, we have outlined the role of genes involved in repair processes and in checkpoint control, with specific reference to genes regulating radiation-sensitivity. Specific examples are provided concerning the use of both yeasts in understanding the mechanism of action of platinum compounds and topoisomerase inhibitors. The availability of the genomic sequence of these organisms as well as of new technologies (microarrays, proteomics) is expected to allow the identification of potential drug targets, since the drug discovery process is moving toward a genomic orientation. Among eukaryotic organisms, yeasts are suitable for easy genetic manipulations, and specific genetic alterations are exploitable for assessing the effects of chemotherapeutic agents with different mechanism of action. Although still at an early stage, this fast-moving field shows promise as a novel and potentially useful method for development of target-specific therapeutic approaches.
Insights
Yeast models, like fission yeast (Schizosaccharomyces pombe) and budding yeast (Saccharomyces cerevisiae), are powerful tools for understanding DNA repair and cell cycle control. Their genetic tractability aids in identifying drug targets and mechanisms of action for novel cancer therapies.
Area of Science:
- Molecular Biology
- Genetics
- Pharmacology
Background:
- Yeast models (Schizosaccharomyces pombe, Saccharomyces cerevisiae) are crucial for studying eukaryotic cellular functions.
- Conserved signaling pathways in yeast and mammals make them ideal for cancer drug research.
Purpose of the Study:
- To explore yeast as a model system for identifying mechanisms of sensitivity to antitumor drugs.
- To highlight the utility of yeast in understanding drug action and discovering new therapeutic targets.
Main Methods:
- Genetic manipulation of yeast to study DNA repair and cell cycle control.
- Utilizing genomic and proteomic technologies for drug target identification.
- Assessing chemotherapeutic agent effects through specific genetic alterations in yeast.
Main Results:
- Yeast genes involved in DNA repair and checkpoint control, particularly radiation sensitivity genes, have been identified.
- Specific examples demonstrate yeast's role in elucidating platinum compounds and topoisomerase inhibitor mechanisms.
- Genomic orientation of drug discovery is enhanced by yeast's suitability for genetic studies.
Conclusions:
- Yeast offers a powerful, genetically tractable platform for advancing cancer drug discovery.
- This approach facilitates understanding drug mechanisms and developing targeted therapies.
- Yeast-based research shows significant promise for novel therapeutic strategies.