Cyclin-dependent kinase inhibitor p20 controls circadian cell-cycle timing
- Authors
- Laranjeiro, R., Tamai, T.K., Peyric, E., Krusche, P., Ott, S., and Whitmore, D.
- ID
- ZDB-PUB-130418-5
- Date
- 2013
- Source
- Proceedings of the National Academy of Sciences of the United States of America 110(17): 6835-40 (Journal)
- Registered Authors
- Laranjeiro, Ricardo, Peyric, Elodie, Tamai, Takako Katherine, Whitmore, David
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Base Sequence
- Brain/metabolism
- Cell Line
- Circadian Rhythm/genetics*
- Circadian Rhythm/physiology
- Computational Biology
- Cyclin-Dependent Kinase Inhibitor Proteins/genetics
- Cyclin-Dependent Kinase Inhibitor Proteins/metabolism*
- Cyclin-Dependent Kinase Inhibitor p21/metabolism
- DNA Replication/genetics*
- DNA Replication/physiology
- Flow Cytometry
- G1 Phase Cell Cycle Checkpoints/genetics*
- G1 Phase Cell Cycle Checkpoints/physiology
- Immunohistochemistry
- In Situ Hybridization
- Likelihood Functions
- Microscopy, Fluorescence
- Models, Genetic
- Molecular Sequence Data
- Nocodazole
- Phylogeny
- Protein Structure, Tertiary
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Alignment
- Sequence Analysis, DNA
- Time Factors
- Zebrafish/genetics*
- Zebrafish/physiology
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 23569261 Full text @ Proc. Natl. Acad. Sci. USA
Specific stages of the cell cycle are often restricted to particular times of day because of regulation by the circadian clock. In zebrafish, both mitosis (M phase) and DNA synthesis (S phase) are clock-controlled in cell lines and during embryo development. Despite the ubiquitousness of this phenomenon, relatively little is known about the underlying mechanism linking the clock to the cell cycle. In this study, we describe an evolutionarily conserved cell-cycle regulator, cyclin-dependent kinase inhibitor 1d (20 kDa protein, p20), which along with p21, is a strongly rhythmic gene and directly clock-controlled. Both p20 and p21 regulate the G1/S transition of the cell cycle. However, their expression patterns differ, with p20 predominant in developing brain and peak expression occurring 6 h earlier than p21. p20 expression is also p53-independent in contrast to p21 regulation. Such differences provide a unique mechanism whereby S phase is set to different times of day in a tissue-specific manner, depending on the balance of these two inhibitors.