Abstract

The G1/S transition represents the stage in the cell cycle when cells either commit to mitosis and continue to proliferate, or embark on developmental pathways in response to environmental and internal cues. In the model yeast S. cerevisiae , the CDK Cdc28p and G1 cyclin Cln3p control passage through the G1/S transition by activating the transcription factor complex SBF/MBF, which is composed of the regulatory subunit Swi6p and the DNA-binding elements Swi4p (SBF) or Mbp1p (MBF). SBF/MBF in turn activates transcription of numerous genes to initiate cell proliferation. In the multi-morphic fungal pathogen C. albicans , the G1/S regulatory circuit and control of basic cell proliferation are poorly understood. Previously work demonstrated that the cyclin Cln3p was essential for growth of yeast cells but also linked to development of hyphae. To gain more insight on the circuitry governing the G1/S transition and identify potential mediators of Cln3p function, we obtained transcription profiles of cells depleted of Cln3p and characterized orthologues of Swi6p, Swi4p and Mbp1p. Our results confirmed that cells depleted of Cln3p were arrested in G1 phase, and provide the first picture of factors associated with the G1/S transition in white phase yeast cells. The data demonstrate that the emerging G1/S circuit contains unique features compared to those in other fungi, including the fact that Cln3p activity is mediated only in part by MBF, that Mbp1p does not playa significant role in regulating yeast cell proliferation, and that novel, fungal-specific factors may be associated with growth control. The data also identify potential factors involved in linking Cln3p and MBF activity with development of hyphae and possibly the opaque yeast state, through novel means. Overall, our results have laid the groundwork for constructing a framework of the G1/S regulatory circuit in C. albicans yeast cells, which will lead to a more comprehensive understanding of how basic cell proliferation in the pathogen is regulated and potentially linked with development, an important virulence-determining trait