title: Systematic Mapping of Chemical-Genetic Interactions in Saccharomyces cerevisiae.
abstract: Chemical-genetic interactions (CGIs) describe a phenomenon where the effects of a chemical compound (i.e., a small molecule) on cell growth are dependent on a particular gene. CGIs can reveal important functional information about genes and can also be powerful indicators of a compound's mechanism of action. Mapping CGIs can lead to the discovery of new chemical probes, which, in contrast to genetic perturbations, operate at the level of the gene product (or pathway) and can be fast-acting, tunable, and reversible. The simple culture conditions required for yeast and its rapid growth, as well as the availability of a complete set of barcoded gene deletion strains, facilitate systematic mapping of CGIs in this organism. This process involves two basic steps: first, screening chemical libraries to identify bioactive compounds affecting growth and, second, measuring the effects of these compounds on genome-wide collections of mutant strains. Here, we introduce protocols for both steps that have great potential for the discovery and development of new small-molecule tools and medicines.
authors: Stanford Genome Technology Center, Department of Biochemistry, Stanford University, Palo Alto, California 94304;
authors: Sundari
authors: S
authors: Suresh
authors: Stanford Genome Technology Center, Department of Biochemistry, Stanford University, Palo Alto, California 94304;
authors: Ulrich
authors: U
authors: Schlecht
authors: Stanford Genome Technology Center, Department of Biochemistry, Stanford University, Palo Alto, California 94304;
authors: Weihong
authors: W
authors: Xu
authors: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California 95064;
authors: Walter
authors: W
authors: Bray
authors: Stanford Genome Technology Center, Department of Biochemistry, Stanford University, Palo Alto, California 94304;
authors: Molly
authors: M
authors: Miranda
authors: Stanford Genome Technology Center, Department of Biochemistry, Stanford University, Palo Alto, California 94304;
authors: Ronald W
authors: RW
authors: Davis
authors: Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors: Corey
authors: C
authors: Nislow
authors: Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors: Guri
authors: G
authors: Giaever
authors: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California 95064;
authors: R Scott
authors: RS
authors: Lokey
authors: Stanford Genome Technology Center, Department of Biochemistry, Stanford University, Palo Alto, California 94304;
authors: Robert P
authors: RP
authors: St Onge
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development*; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D054852:Small Molecule Libraries