Steve Haase, an Associate Professor of Biology from Duke University will deliver a lecture on "Cycling Without Cyclins: A Transcriptional Network Oscillator"
The cyclin/CDK system is widely viewed as the master oscillator driving cell-cycle events. However, we have demonstrated that the majority of the cell-cycle-regulated transcriptional program remains periodic in budding yeast cells arrested at the G1/S border by depletion of all S-phase and Mitotic cyclins. These results (and others) led us to propose that the cell-cycle transcriptional program is intrinsically controlled by a cascading network of serially activated transcription factors functioning as an autonomous oscillator, independent of cyclin/CDKs, and cell-cycle progression. The cyclin/CDK system and the transcriptional network oscillator are coupled at multiple points. Cyclins, along with various key cell-cycle regulators, are periodically transcribed by factors in the transcription network; and in turn, cyclin/CDKs regulate several of the transcription factors in the network. These findings establish a new paradigm for cell-cycle control in budding yeast. Cell-cycle progression is coordinated by coupling cyclin/CDKs to an autonomous transcriptional network oscillator.
Checkpoints are intracellular signaling pathways that maintain genome stability by inhibiting cyclin/CDK activity, and blocking cell-cycle progression when key events fail to occur according to plan. Our experiments reveal that checkpoint pathways also block the periodic oscillation of the transcriptional network. We hypothesize that checkpoints regulate the dynamics of the cell- cycle-regulated transcriptional program in order to maintain synchrony between the transcriptional program and cell-cycle progression. Taken together, our data suggest that cell-cycle control is achieved by integrating the functions of cyclin/CDKs, checkpoints, and an autonomous transcriptional network oscillator