Cyclin-Dependent Kinases Are Regulators and Effectors of Oscillations Driven by a Transcription Factor Network

Laura A. Simmons Kovacs, Michael B. Mayhew, David A. Orlando, Yuanjie Jin, Qingyun Li, Chenchen Huang, Steven I. Reed, Sayan Mukherjee, Steven B. Haase

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

During embryonic cell cycles, B-cyclin-CDKs function as the core component of an autonomous oscillator. Current models for the cell-cycle oscillator in nonembryonic cells are slightly more complex, incorporating multiple G1, S phase, and mitotic cyclin-CDK complexes. However, periodic events persist in yeast cells lacking all S phase and mitotic B-cyclin genes, challenging the assertion that cyclin-CDK complexes are essential for oscillations. These and other results led to the proposal that a network of sequentially activated transcription factors functions as an underlying cell-cycle oscillator. Here we examine the individual contributions of a transcription factor network and cyclin-CDKs to the maintenance of cell-cycle oscillations. Our findings suggest that while cyclin-CDKs are not required for oscillations, they do contribute to oscillation robustness. A model emerges in which cyclin expression (thereby, CDK activity) is entrained to an autonomous transcriptional oscillator. CDKs then modulate oscillator function and serve as effectors of the oscillator.

Original languageEnglish
Pages (from-to)669-679
Number of pages11
JournalMolecular cell
Volume45
Issue number5
DOIs
StatePublished - Mar 9 2012

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