Breeden, Linda

Our focus is to understand how the commitment to the mitotic cell cycle is regulated in response to environmental and internal cues. Much of the work of the last decade has involved studying the cell cycle in rapidly growing cells with abundant nutrients. We have begun to investigate a far more common transition, which is the transition of quiescent, non-dividing yeast cells back into the cell cycle. The critical transitions in the eukaryotic cell cycle are controlled by cyclin-dependent kinases (CDKs). In budding yeast, as in all higher eukaryotes, the decision to enter quiescence or to commit to another division cycle occurs in G1. There are three G1 cyclins (Cln1,2 and 3) that play critical roles in modulating the decision to enter the cell cycle. All three of these cyclins are regulated at the transcription level. We have been investigating the mechanisms of transcriptional regulation of these cyclins and its impact on cell cycle progression. One outcome of these studies is a systematic analysis of cell cycle regulated transcripts in budding yeast (see below). By comparing our budding yeast data to that of fission yeast and humans, we have identified 72 genes whose periodic transcription may be conserved through evolution. These genes are highly enriched for cell cycle genes and they are eight times more likely to be Cdk targets. Using computational approaches, we have also identified two novel mechanisms of cell cycle-specific transcription. M/G1-specific transcription is imposed by the association of a pair of homeobox repressors with Mcm1 at ECB elements. S phase-specific transcription of a group of genes involved in chromosome segregation is activated by the Hcm1 transcription factor.