Genomes and Genes
CELL CYCLE REGULATION OF THE YEAST HO GENE
Principal Investigator: LINDA BREEDEN
Abstract: The mechanisms that control the cell cycle are remarkably conserved among all eukaryotes. The decision to commit to a round of cell division occurs in G1 in most organisms and oncogenic processes exert their greatest impact by interfering with regulators of G1 progression. Our research is focused on the molecular mechanisms that control the decision to enter the mitotic cell cycle in growing and quiescent cells. The control of the G1 to S transition is governed by cyclin-dependent kinases (Cdks). In budding yeast, there are three G1 cyclins that are transcriptionally regulated in two consecutive waves. The first wave of transcription produces components the Cln3 cyclin and the transcription factor Swi4. During early G1, Cln3 activates the cyclin-dependent kinase (Cdk), which, in turn activates the Iate-G1 transcription complexes, Swi6/Swi4 and Swi6/Mbp1. These complexes regulate over 200 transcripts, including the late G1 wave of cyclin production, which is key to the transition to S phase. Now more than ever, the mechanism of late G1 transcription resembles the metazoan pathway, in that the yeast equivalent of Retinoblastoma (Rb) has been identified. This protein, Whi5, represses late G1 transcription and can be phosphorylated and released from the transcription complex by Cln3/Cdk phosphorylation. We propose to establish the relationships between the late G1 transcription complex components and Whi5 and to identify how the activities of these components are affected by the signaling pathways that influence Start in response to intrinsic and extrinsic cues. This is important in rapidly growing cells, but it is equally important to understand the modifications of the Start program that enable cells to enter, maintain and recover from quiescence, because this is the more prevalent transition outside the laboratory. Most cells exit the cycle from G1. To do so, the mitotic Start machinery must be stably inactivated and then reactivated when conditions improve. For the first time, we are able to purify a uniform population of GO cells that synchronously enter S phase from GO. We will use this method to test a series of mutants that deregulate the mitotic start program to see how GO to S and G1 to S differ.
Funding Period: ----------------1988 - ---------------2011-
more information: NIH RePORT