Expression profiling of the response of Saccharomyces cerevisiae to 5-fluorocytosine using a DNA microarray.

5-Fluorocytosine is a commonly used antifungal agent. It acts by inhibiting the synthesis of fungal DNA and protein. In order to understand the global response of Saccharomyces cerevisiae to changes in DNA and protein synthesis caused by 5-fluorocytosine, genome-wide transcript profiling following 5-fluorocytosine exposure was obtained. A total of 96 genes were identified as responsive to 25 microg/ml fluorocytosine treatment for 90 min, which caused approximately 17% specific growth inhibition. The transcript levels of 57 genes were increased more than 2-fold, while it was found that the transcript levels of the other 39 genes decreased to a similar extent. Genes involved in DNA repair, synthesis and replication represented the highest proportion of induced genes identified, which may account for the easily acquired resistance to 5-fluorocytosine. Two enzyme encoding genes CTS1 and EGT2, which function in the separation of daughter cells from their mother cells, were down-regulated by a factor of 3.7 and 10.2, respectively, indicating that 5-fluorocytosine may also inhibit the separation of fungal cells. Copyright 2002 Elsevier Science B.V. and International Society of Chemotherapy