A PDR5-independent pathway of multi-drug resistance regulated by the SIN4 gene product.

The SIN4 locus encodes a global transcriptional regulator of various yeast genes. In this report, we demonstrate that loss of function mutations in SIN4 create a multi-drug hypersensitive phenotype that is independent of PDR5 mediated resistance. Thus, double sin4, pdr5 mutants are more sensitive than single mutants. Furthermore, SIN4 does not regulate the PDR5 locus. These observations establish that yeast cells have two genetically distinct pathways conferring resistance towards similar substrates.