Cdc1 and the Vacuole Coordinately Regulate Mn²⁺ Homeostasis in the Yeast Saccharomyces cerevisiae

Corresponding author: Stephen Garrett, Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical Center, 185 South Orange Ave., University Heights, Newark, NJ 07103-2714, garretst{at}umdnj.edu (E-mail).

Communicating editor: M. JOHNSTON

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 cos16 deletion strain, and a cdc1 cos16 double mutant exhibits robust growth on medium supplemented with Mn²⁺. Thus, the single, essential function of Cdc1 is to regulate intracellular, probably cytosolic, Mn²⁺.

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