| dc.description.abstract |
<p>The cell division cycle is the process in which the entirety of a cell's contents
is duplicated completely and then equally segregated into two identical daughter cells.
The order of the steps in the cell cycle must be followed with fidelity to guarantee
two viable cells. Understanding the regulatory mechanisms that control cell-cycle
events remains to be a fundamental question in cell biology. In this dissertation,
I explore the mechanisms that coordinate and regulate cell-cycle progression in the
budding yeast, Saccharomyces cerevisiae.</p><p>Cell-cycle events have been shown to
be triggered by oscillations in the activity of cyclin dependent kinases (CDKs) when
bound to cyclins. However, several studies have shown that some cell-cycle events,
such as periodic transcription, can continue in the absence of CDK activity. How are
periodic transcription and other cell-cycle events coupled to each other during a
wild-type cell cycle? Currently, two models of cell-cycle regulation have been proposed.
One model hypothesizes that oscillations in CDK activity controls the timing of cell-cycle
events, including periodic transcription. The second model proposes that a transcription
factor (TF) network oscillator controls the timing of cell-cycle events, via proper
timing of gene expression, including cyclins. By measuring global gene expression
dynamics in cells with persistent CDK activity, I show that periodic transcription
continues. This result fits with the second model of cell-cycle regulation. Further,
I show that during a wild-type cell cycle, checkpoints are responsible for arresting
the bulk of periodic transcription. This finding adds a new layer of regulation to
the second model, providing a mechanism that coordinates cell-cycle events with a
TF network oscillator. Taken together, these data provide further insight into the
regulation of the cell cycle.</p>
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