Cell Cycle Control System
The cell-cycle control system is a network of regulatory proteins that triggers and coordinates the events of the cycle and verifies their completion before allowing progression.
Definition
The cell-cycle control system is the set of cyclin-dependent kinases and their regulators and checkpoints that determines when the cell advances through each phase of the cycle.
Scope
This topic covers the cyclin and cyclin-dependent kinase machinery that drives cell-cycle transitions, the regulation of this machinery by cyclin synthesis and destruction, phosphorylation, and inhibitors, and the checkpoints that monitor DNA integrity, replication, and chromosome attachment.
Core questions
- How do cyclins and cyclin-dependent kinases time cell-cycle transitions?
- How is cyclin-dependent kinase activity turned on and off?
- What do the major checkpoints monitor?
- How does the system ensure events occur once and in the correct order?
Key theories
- Cyclin–CDK oscillator
- Cyclin-dependent kinase activity oscillates as cyclins are periodically synthesized and abruptly destroyed, and these oscillations drive the ordered transitions of the cell cycle.
- Checkpoint control
- Surveillance mechanisms detect problems such as DNA damage or incomplete replication and halt the cycle until they are resolved, ensuring the order and fidelity of cell-cycle events.
Mechanisms
Cyclin-dependent kinases are active only when bound to cyclins, whose levels rise and fall through the cycle; activating and inhibitory phosphorylations and CDK inhibitor proteins further tune activity. Different cyclin–CDK complexes drive entry into S phase and into mitosis, and targeted destruction of cyclins by the ubiquitin–proteasome system makes transitions irreversible. Checkpoints at the G1/S, G2/M, and metaphase-to-anaphase transitions sense readiness and damage, blocking CDK activity or anaphase onset until conditions are satisfied.
Clinical relevance
The control system explains how cells regulate proliferation with high fidelity and is a central model for understanding cellular regulation. The treatment here is descriptive and non-prescriptive.
History
Hunt's discovery of cyclins and Nurse's identification of the central cyclin-dependent kinase revealed the engine of the cycle, while Hartwell's checkpoint concept explained how order and fidelity are enforced, framing the modern control system.
Key figures
- Leland Hartwell
- Paul Nurse
- Tim Hunt
- David Morgan
Related topics
Seminal works
- evans1983
- hartwell1989
Frequently asked questions
- Why must cyclins be destroyed?
- Destroying cyclins switches off the corresponding kinase activity, making each transition irreversible and resetting the system so the next phase can proceed in order.
- What happens at a checkpoint if something is wrong?
- The checkpoint blocks further progression, for example by inhibiting cyclin-dependent kinase activity or delaying chromosome separation, until the problem such as DNA damage is corrected.