<p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p> <p>Understanding the actions of drugs and toxins in a cell is of critical importance
to medicine, yet many of the molecular events involved in chemical resistance are
relatively uncharacterized. In order to identify the cellular processes and pathways
targeted by chemicals, we took advantage of the haploid <italic>Saccharomyces cerevisiae</italic>
deletion strains (Winzeler <italic>et al.,</italic> 1999). Although ~4800 of the strains are viable,
the loss of a gene in a pathway affected by a drug can lead to a synthetic lethal
effect in which the combination of a deletion and a normally sublethal dose of a
chemical results in loss of viability. WE carried out genome-wide screens to determine
quantitative sensitivities of the deletion set to four chemicals: hydrogen peroxide,
menadione, ibuprofen and mefloquine. Hydrogen peroxide and menadione induce
oxidative stress in the cell, whereas ibuprofen and mefloquine are toxic to yeast by
unknown mechanisms. Here we report the sensitivities of 659 deletion strains that
are sensitive to one or more of these four compounds, including 163 multichemicalsensitive
strains, 394 strains specific to hydrogen peroxide and/or menadione, 47
specific to ibuprofen and 55 specific to mefloquine.We correlate these results with data
from other large-scale studies to yield novel insights into cellular function.</p>
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Comp Funct Genomics. 2004 Apr; 5(3):216-224