Saccharomyces cerevisiae can adapt to growth under severe oxygen limitation by initiating a complex genetic and biochemical program that enable the cell to adjust their metabolism accordingly in order to survive. We have been engaged in elucidating the regulatory pathway of a specialized set of proteins that are expressed exclusively during anaerobic growth. We are interested in understanding the molecular mechanism by which these proteins are turned on in anaerobic cells and at the same time how they are kept repressed in the presence of oxygen. In the course of our study we have identified several regulatory factors which control this adaptive response. We are using molecular genetics and biochemical analyses to delineate the mechanisms of activation and repression of these anaerobic proteins. Some of these factors have been shown to be upregulated in cells with reduced susceptibility to azoles, drugs that target sterol biosynthesis while others when they are inhibited, the cells become susceptible to these drugs. This work will further our knowledge on what might be considered a type of metabolically induced differentiation and could open up a fairly extensive area of inquiry, possibly in antifungal drug development.
| Sertil, Odeniel; Vemula, Arvind; Salmon, Sharon L et al. (2007) Direct role for the Rpd3 complex in transcriptional induction of the anaerobic DAN/TIR genes in yeast. Mol Cell Biol 27:2037-47 |
