Mutations in the Saccharomyces cerevisiae gene SAC1 cause multiple drug sensitivity.
Wild-type yeast Saccharomyces cerevisiae are surprisingly resistant to a wide range of drugs and agents. We had previously isolated novobiocin-sensitive mutants to aid the study of the intracellular target for this drug. Characterization of one of these mutants, mds1, revealed that it was sensitive not only to novobiocin but also to a wide range of drugs. The nature of this multiple drug-sensitive phenotype was shown to be different from that of previously isolated multiple drug-sensitive mutants. We have shown that the multiple drug-sensitivity of mds1 is due to mutations within the gene SAC1 and have identified a variety of mutations within the gene from the Mds1 strain. SAC1 encodes a protein which has been previously implicated in the correct function of the actin cytoskeleton, in inositol metabolism, in ATP transport in the endoplasmic reticulum and in Sec14p (PI-TP) function. We have shown that multiple drug-sensitivity is a new phenotype seen in some, but not all, of the previously characterized sac1 mutants. Based on our findings, we propose a mechanism by which Sac1p could affect drug resistance and also mediate other effects on cell growth.
Hughes
W E
WE
Department of Cell Biology, GlaxoWellcome, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, U.K. hughesw@icrf.icnet.uk
Pocklington
M J
MJ
Orr
E
E
Paddon
C J
CJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000502:physiology; D017931:DNA Primers / Q000737:chemistry; D004271:DNA, Fungal / Q000737:chemistry; D004352:Drug Resistance, Microbial / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009675:Novobiocin / Q000494:pharmacology*; D010641:Phenotype; D010957:Plasmids / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014170:Transformation, Genetic
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D017931:DNA Primers; D004271:DNA, Fungal; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C099636:Sac1 protein, Chlamydomonas reinhardtii; D009675:Novobiocin