Cdc1 and the vacuole coordinately regulate Mn2+ homeostasis in the yeast Saccharomyces cerevisiae

The yeast CDC1 gene encodes an essential protein that has been implicated in the regulation of cytosolic [Mn2+]. To identify factors that impinge upon Cdc1 or the Cdc1-dependent process, we isolated second-site suppressors of the conditional cdc1-1(Ts) growth defect. Recessive suppressors define 15 COS (CdcOne Suppressor) genes. Seven of the fifteen COS genes are required for biogenesis of the vacuole, an organelle known to sequester intracellular Mn2+. An eighth gene, COS16, encodes a vacuolar membrane protein that seems to be involved in Mn2+ homeostasis. These results suggest mutations that block vacuolar Mn2+ sequestration compensate for defects in Cdc1 function. Interestingly, Cdc1 is dispensable in a cos16delta deletion strain, and a cdc1delta cos16delta double mutant exhibits robust growth on medium supplemented with Mn2+. Thus, the single, essential function of Cdc1 is to regulate intracellular, probably cytosolic, Mn2+.