Identification of yeast deletion strains that are hypersensitive to brefeldin A or monensin, two drugs that affect intracellular transport.
We have screened the Eurofan deletion strain collection for mutants that are either sensitive or resistant to three drugs known to affect intracellular transport: brefeldin A, monensin and C(2)-ceramide. Drug-sensitive mutants were analysed by complementation with cognate clones and tetrad analysis to confirm that the phenotypes are linked to the deletions. Out of 620 deletion strains, we found 18 mutants that were sensitive to either brefeldin A, monensin or both. Several of these mutants are deleted for genes that are known to be involved in intracellular transport, membrane biogenesis and/or cell wall biosynthesis. Among such previously known genes were VAM6, VAC7, SYS1, TLG2, RCY1, ERG4, ALG9 and ALG12. Some other genes recovered in our screen were not previously implicated in intracellular transport, but are related to other yeast genes with such a function. Still other genes encode proteins with no obvious link to intracellular transport. Several of these are putative transcription factors or RNA-binding proteins, which suggests that they may affect drug sensitivity by modulating the expression of other genes or proteins.
Murén
E
E
Department of Plant Biology, Uppsala Genetic Center, Swedish University of Agricultural Sciences, Box 7080, S-750 07 Uppsala, Sweden.
Oyen
M
M
Barmark
G
G
Ronne
H
H
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology*; D002462:Cell Membrane / Q000235:genetics; D002473:Cell Wall / Q000235:genetics; D017353:Gene Deletion; D005800:Genes, Fungal; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D015003:Yeasts / Q000187:drug effects* / Q000235:genetics
D000935:Antifungal Agents; D020126:Brefeldin A