Transcriptional control of gene expression during the G2-M phase of the cell cycle

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The division of eukaryotic cells into two daughter cells is coordinately regulated. This division process takes from between 1 hour in yeasts to up to 24 hours in humans. Over this period a series of events is initiated in a process called the cell cycle whereby one event leads to another, and ultimately culminates in cell division and then reinitiation of the whole process. To regulate this process, there are numerous control points in the cell cycle. One of the major control points is following DNA replication and before the cells commit to division (the G2-M control point). This control point is at least partially regulated at the level of transcription, the process by which genes are turned on and their code deciphered and converted to first RNA and the protein. This project aims to study how transcription at this key control point is regulated. We will use the model organism S. Cerevisiae (budding yeast) which shows a remarkable conservation of cell cycle control mechanisms with higher organisms such as humans. We know the key regulators (transcription factors) that act at this control point, and how they themselves can be regulated through modification by a process known as phosphorylation. However, what we do not know is how the transcription factors regulate transcription. Furthermore, we do not know how subtly different activation events occur at this control point. ie not all genes are activated with the same temporal kinetics. We aim to study the molecular details of how transcription factors function to regulate target gene transcription and how these transcription factors are themselves controlled. We anticipate that the findings we make in our model system will be directly relevant to other systems. Indeed the deregulation of cell cycle control is a pre-requisite for tumourigenesis, therefore our studies may impact on our understanding of and ability to combat cancer.