Transcription network and cyclin/CDKs: The yin and yang of cell cycle oscillators

AbstractIt is widely accepted that the central cell cycle oscillator is based on cyclin/CDK complexes. In a recent study, we challenged this model, and showed that a transcription factor network can drive correctly-timed periodic events independent of cyclin/CDK functions1. The transcription factor network oscillator was revealed in budding yeast cells deleted for all six B-cyclin genes. These cells undergo successive rounds of budding2, and continue to activate the bulk of the cell-cycle-regulated genes on schedule, even though they are unable to replicate DNA or enter mitosis1. These findings led us to propose that the cell cycle is regulated by the coupled activities of a transcription network oscillator and the CDK oscillator. Here, we discuss the transcription network oscillator in the context of the historical view that CDKs form the central cell cycle oscillator. We also discuss the role of transcription networks in controlling temporal programs in a variety of biological systems and their ability to function as oscillators. Finally, we consider how the transcription network oscillator collaborates with CDKs and checkpoint mechanisms to control the ordered events of the cell cycle.