👤 P Sudbery

In Saccharomyces cerevisiae, the G1 cyclin Cln3 initiates the Start of a mitotic cell cycle in response to size and nutrient inputs. Loss of Cln3 delays but does not prevent Start, due to the eventual Cln3-independent transcription of CLN1 and CLN2. When unbudded cells of the human pathogen Candida albicans were depleted of the G1 cyclin Cln3 they increased in size but did not bud. Thus, unlike S. cerevisiae, Cln3 is essential for budding in C. albicans. However, eventually the large unbudded cells spontaneously produced filamentous forms. The morphology was growth medium dependent; on nutritionally poor medium the polarized outgrowths fulfilled the formal criteria for true hyphae. This state is stable, and continued growth leads to a hyphal mycelium, which invades the agar substratum. Interestingly, it is also required for normal hyphal development, as Cln3-depleted cells develop morphological abnormalities if challenged with hyphal inducing signals such as serum or neutral pH. Taken together, these results show that, in C. albicans, Cln3 has assumed a critical role in coordinating mitotic cell division with differentiation. Show less

Wild-type cells of the budding yeast Saccharbmyces cerevisiae arrest in G1 upon nutrient exhaustion. Cell cycle arrest requires the WHI2 gene since whi2 mutants continue to divide and become abnormally small as nutrients are depleted. Here we show that CLN1 and CLN2 transcript levels in a whi2 strain are higher during exponential growth, and persist longer upon starvation, than in an isogenic wild-type strain. In contrast to CLN1 and CLN2, CLN3 levels declined only at very high cell density and were unaffected by the whi2 mutation. Elevated CLN expression is sufficient to explain the whi2 phenotype since ectopic expression of CLN1 in a nutrient-depleted culture caused cells to continue dividing and interfered with the acquisition of heat resistance. These observations show that, either directly or indirectly, Whi2 negatively regulates G1 cyclin expression. Interestingly extremely high levels of Cln1 induced filamentous growth upon nutrient deprivation, suggesting a direct connection between G1 cyclin activity and morphological responses to poor nutrient conditions. Show less