| Summary: | Systematic genomic studies in the budding yeast S. cerevisiae have greatly increased our
capacity to conduct functional profiling of the eukaryotic genome. I describe a new method that
makes use of yeast “Barcoder” strains to uniquely tag strains in a yeast overexpression collection
(FLEX) and to systematically examine the effects of gene overexpression on cell fitness. This
novel system is compatible with the so-called Synthetic Genetic Array (SGA) method, which
automates yeast genetics and allows introduction of marked query alleles of interest into arrayed
collections of yeast mutants. I identified SDL interactions for two key regulatory kinases, Dun1
and Mck1, using my system. I also used my array and approach to identify SDL interactions for
Dun1 that are only manifest in the presence of DNA damage. These studies demonstrate the
utility of the pooled SGA-SDL method for systematic discovery of condition-specific genetic
interactions in conserved biological pathways.
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