Related Experiment Video
Updated: May 15, 2026
06:53
Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
NONO couples the circadian clock to the cell cycle
Elzbieta Kowalska1, Juergen A Ripperger, Dominik C Hoegger
1Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland.
Summary
The nuclear protein NONO links circadian rhythms to the cell cycle, impacting cell proliferation and wound healing. Its absence disrupts cell cycle control and impairs tissue repair in mice.
Area of Science:
- Cell Biology
- Chronobiology
- Molecular Biology
Background:
- Mammalian circadian clocks regulate cell proliferation, but the underlying mechanisms remain unclear.
- The multifunctional nuclear protein NONO interacts with circadian PERIOD (PER) proteins.
Purpose of the Study:
- To investigate the role of NONO in circadian gating of the cell cycle.
- To elucidate the molecular mechanisms connecting NONO, PER proteins, and cell cycle regulation.
- To determine the in vivo significance of this connection for tissue repair.
Main Methods:
- Fibroblast analysis from NONO-deficient mice.
- Molecular analysis of NONO binding to the p16-Ink4A gene.
- Assessment of circadian gene expression and cell cycle gating.
- In vivo wound healing assays in mice.
Main Results:
- NONO deficiency led to increased cell doubling and reduced senescence in fibroblasts.
- NONO potentiated circadian activation of the p16-Ink4A cell cycle checkpoint gene in a PER-dependent manner.
- Loss of NONO or PER abolished p16-Ink4A circadian expression and cell cycle gating.
- NONO-deficient mice exhibited impaired wound healing.
Conclusions:
- NONO is crucial for coupling the cell cycle to the circadian clock.
- This coupling regulates cell proliferation and is essential for effective wound healing.
- Disrupting this link has significant implications for tissue organization and repair.
Related Concept Videos
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
02:19Circadian Rhythms and Gene Regulation
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
01:28The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
02:45Biological Clocks and Seasonal Responses
The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.