TY - JOUR
T1 - Cyclin-Dependent Kinases Are Regulators and Effectors of Oscillations Driven by a Transcription Factor Network
AU - Simmons Kovacs, Laura A.
AU - Mayhew, Michael B.
AU - Orlando, David A.
AU - Jin, Yuanjie
AU - Li, Qingyun
AU - Huang, Chenchen
AU - Reed, Steven I.
AU - Mukherjee, Sayan
AU - Haase, Steven B.
N1 - Funding Information:
We thank J. Harer, D. Lew, M. Clyde, and members of the Haase lab for helpful discussions. We also thank D. Lew, S. Bristow, A. Leman, and C. Lin for critical reading of the manuscript and M. Chee for supplying plasmids and technical advice. This work was supported by the National Institutes of Health, NIH P50-GM081883 (Duke Center for Systems Biology). C.H. was supported by funds from Grant#52005871 to Duke University from the Howard Hughes Medical Institute.
PY - 2012/3/9
Y1 - 2012/3/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84862821535&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2011.12.033
DO - 10.1016/j.molcel.2011.12.033
M3 - Article
C2 - 22306294
AN - SCOPUS:84862821535
SN - 1097-2765
VL - 45
SP - 669
EP - 679
JO - Molecular cell
JF - Molecular cell
IS - 5
ER -