MOLECULAR-CLONING AND ANALYSIS OF CDC28 AND CYCLIN HOMOLOGS FROM THE HUMAN FUNGAL PATHOGEN CANDIDA-ALBICANS

In the budding yeast Saccharomyces cerevisiae, progress of the cell cy cle beyond the major control point in G1 phase, termed START, requires activation of the evolutionarily conserved Cdc28 protein kinase by di rect association with G1 cyclins. We have used a conditional lethal mu tation in CDC28 of S. cerevisiae to clone a functional homologue from the human fungal pathogen Candida albicans. The protein sequence, dedu ced from the nucleotide sequence, is 79% identical to that of S. cerev isiae Cdc28 and as such is the most closely related protein yet identi fied. We have also isolated from C. albicans two genes encoding putati ve G1 cyclins, by their ability to rescue a conditional G1 cyclin defe ct in S. cerevisiae; one of these genes encodes a protein of 697 amino acids and is identical to the product of the previously described CCN I gene. The second gene codes for a protein of 465 residues, which has significant homology to S. cerevisiae Cln3. These data suggest that t he events and regulatory mechanisms operating at START are highly cons erved between these two organisms.