In Controlling the Cell Cycle you met checkpoints, the places where a cell decides whether to go on. The decisions are made by proteins whose levels and activity change through the cycle, using the same kinase switches as signal pathways.
- Cyclin-dependent kinases (CDKs) are enzymes that phosphorylate target proteins to push the cell into the next phase. Their amount stays fairly steady.
- Cyclins are proteins whose levels rise and fall. A CDK works only when bound to its cyclin. When a cyclin is destroyed, its CDK goes quiet.
- One cyclin-CDK pair, called MPF (maturation-promoting factor, also read as M-phase-promoting factor), peaks at the end of G₂ and drives the cell into mitosis; its cyclin is destroyed during mitosis.
Key idea
Cyclin levels rise and fall; CDK levels stay steady. A cyclin-CDK complex is active only when enough cyclin is present, and it pushes the cell past a checkpoint. Brakes such as p53 stop the cycle at G₁ when DNA is damaged, allowing repair, or trigger apoptosis (programmed cell death) if the damage is too great.
Why it works
Why build a switch from two parts? Making and destroying a small protein (cyclin) is a quick, clean way to switch a big enzyme on and off. Destroying cyclin also makes the cycle run one way: the cell cannot slip back into the phase it just left. Checkpoints add safety: a cell copies DNA only if conditions are right (G₁), divides only after copying is complete and correct (G₂), and separates chromosomes only when all are attached to the spindle (M).
Worked examples
Worked example: Reading the graph
Using the graph, at which point in the cycle is MPF most active, and why does its activity drop suddenly?
- MPF activity peaks at the same time as mitotic cyclin, at the end of G₂.
- Its CDK is present all the time, so the CDK is not what changes.
- During mitosis the cyclin is destroyed, so the CDK has no partner.
Answer: At the G₂-to-mitosis transition. It drops when the cyclin is broken down during mitosis.
Worked example: Losing a brake
A cell has a mutation that destroys its p53 protein. Its DNA is then damaged by radiation. What is likely to happen?
- Normally, damaged DNA raises p53, which halts the cycle at G₁ for repair, or triggers apoptosis.
- Without p53, the cell does not stop.
- It copies and passes on the damaged DNA.
Answer: The cell keeps dividing with damaged DNA, so more mutations build up. Loss of p53 is found in many cancers, which are uncontrolled cell division.
Common mistake
Thinking CDKs come and go through the cycle. The CDK is present all the time; it is the cyclin that rises and falls. That is why the enzyme is called cyclin-dependent: its activity, not its amount, follows the cyclin. On a graph, a flat line is the CDK and a sawtooth is the cyclin.