title: Cyclin-dependent kinase inhibitor p20 controls circadian cell-cycle timing.
abstract: 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.
authors.affiliation: Centre for Cell and Molecular Dynamics, Department of Cell and Developmental Biology, University College London, London WC1E 6DE, United Kingdom.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Laranjeiro
authors.forename: T Katherine
authors.initials: TK
authors.lastname: Tamai
authors.forename: Elodie
authors.initials: E
authors.lastname: Peyric
authors.forename: Peter
authors.initials: P
authors.lastname: Krusche
authors.forename: Sascha
authors.initials: S
authors.lastname: Ott
authors.forename: David
authors.initials: D
authors.lastname: Whitmore
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics* / Q000502:physiology; D019295:Computational Biology; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics* / Q000502:physiology; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics* / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016013:Likelihood Functions; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015739:Nocodazole; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013997:Time Factors; D015027:Zebrafish / Q000235:genetics* / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D029961:Zebrafish Proteins; C581879:cyclin-dependent kinase inhibitor p21, zebrafish; D015739:Nocodazole