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Cell Cycle Checkpoints: Cyclins, CDKs, p53 and Rb
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The cell cycle moves a cell through G1, S, G2 and M. Checkpoints stop it when something is wrong. Cyclin-dependent kinases (CDKs) drive each transition, and p53 and Rb are the brakes whose loss gives cancer.
Phases and checkpoints
| Phase | What happens | Checkpoint |
|---|---|---|
| G1 | Growth, normal function | G1/S: size, nutrients, DNA damage |
| S | DNA replication | Replication completeness |
| G2 | Growth, prepare for mitosis | G2/M: DNA intact and fully copied |
| M | Mitosis and cytokinesis | Spindle checkpoint: all chromosomes attached |
| G0 | Resting or nondividing | Exit from the cycle |
The G1/S checkpoint is the main commitment point. Many differentiated cells, such as neurons, sit in G0.
Cyclins and CDKs
A CDK is always present but inactive. It needs to bind its cyclin, whose concentration rises and falls through the cycle, to become an active kinase that phosphorylates target proteins. Different cyclin-CDK pairs act at different stages, and MPF (cyclin B with CDK1) triggers entry into mitosis.
Tumor suppressors and oncogenes
| Type | Role | Effect of mutation |
|---|---|---|
| Tumor suppressor (p53, Rb) | Brakes | Loss of function causes cancer, both alleles must be lost |
| Proto-oncogene (Ras, cyclins) | Accelerators | Gain of function in a single allele gives an oncogene |
Rb holds the transcription factor E2F in check, so the cell cannot enter S phase. Phosphorylation of Rb by cyclin-CDK releases E2F. DNA damage raises p53, which causes arrest through p21 to allow repair, and triggers apoptosis if the damage cannot be fixed.
Common traps
- Saying cyclin levels are constant. They oscillate, CDK levels do not.
- Mixing up the mutation type. Tumor suppressors need loss of function, oncogenes need gain.
- Placing the spindle checkpoint in G2. It is within M, before anaphase.
- Calling G0 a phase of the cycle. It is an exit from it.
One-minute recap
G1, S, G2, M with checkpoints. Cyclin binds CDK to activate it. Rb blocks E2F until phosphorylated. p53 arrests the cycle or triggers apoptosis. Tumor suppressors: loss of function. Oncogenes: gain of function.
Check yourself: 5-question mini-quiz
1. What activates a CDK?
Binding to its cyclin, whose levels rise and fall through the cycle.
2. What does p53 do after DNA damage?
It halts the cycle for repair, and triggers apoptosis if repair fails.
3. What does Rb do in its unphosphorylated form?
It binds E2F and blocks entry into S phase.
4. Which checkpoint ensures all chromosomes are attached to spindle fibers?
The spindle checkpoint in M phase, before anaphase.
5. Which type of mutation activates a proto-oncogene?
A gain of function, and one mutated allele is enough.
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