Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 17, Pages 6835-6840Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1217912110
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Funding
- Biotechnology and Biological Sciences Research Council (BBSRC)
- ERASysBio+ Grant [BB/I004823/1]
- Fundacao para a Ciencia e a Tecnologia [SFRH/BD/63863/2009]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/63863/2009] Funding Source: FCT
- Biotechnology and Biological Sciences Research Council [BB/I004521/1, BB/I003592/1, BB/I004823/1] Funding Source: researchfish
- BBSRC [BB/I003592/1, BB/I004823/1] Funding Source: UKRI
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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.
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