Pleiotropic drug-resistance attenuated genomic library improves elucidation of drug mechanisms.

Identifying Saccharomyces cerevisiae genome-wide gene deletion mutants that confer hypersensitivity to a xenobiotic aids the elucidation of its mechanism of action (MoA). However, the biological activities of many xenobiotics are masked by the pleiotropic drug resistance (PDR) network which effluxes xenobiotics that are PDR substrates. The PDR network in S.

Chemical genetic and chemogenomic analysis in yeast.

Chemogenomics is the systematic genome-wide study of the cellular response to small molecule agents. Modern high-throughput genetic techniques allow massively parallel examination of the genetic effects of such biologically active small molecules (BASM). Here we present methodology for the identification and characterization of potentially bioactive compounds using the budding yeast Saccharomyces cerevisiae as a model organism.

Laulimalide and peloruside A inhibit mitosis of Saccharomyces cerevisiae by preventing microtubule depolymerisation-dependent steps in chromosome separation and nuclear positioning.

The activity and mechanism of action of two microtubule-stabilising agents, laulimalide and peloruside A, were investigated in Saccharomyces cerevisiae. In contrast to paclitaxel, both compounds displayed growth inhibitory activity in yeast with wild type TUB2 and were susceptible to the yeast pleiotropic drug efflux pumps, as evidenced by the increased sensitivity of a pump transcription factor knockout strain, pdr1Δpdr3Δ. Laulimalide (IC50=3.