AP® Biology review sheet from Aim for Five (aimforfive.com/bio/units/4/4-6)
Unit 4 · Topic 4.6
4.6 Regulation of Cell Cycle
The cell cycle is controlled by checkpoints, which stop the cycle if something is wrong, and by cyclins and cyclin-dependent kinases (CDKs), which push it forward. When these controls are disrupted, a cell may divide out of control and form cancer, or it may be told to undergo apoptosis. This topic ties together cell signaling (4.2–4.3) and the cell cycle (4.5).
Key terms
- checkpoint
- cyclin
- cyclin-dependent kinase (CDK)
- cancer
- apoptosis
Checkpoints
A checkpoint is a control point where the cell checks internal and external signals before moving on. If conditions aren't right, the cycle pauses until the problem is fixed, or the cell is sent to apoptosis.
| Checkpoint | When | What it checks |
|---|---|---|
| G₁ checkpoint | End of G₁, before S | Is the cell big enough, with enough nutrients and growth signals? Is the DNA undamaged? If not, the cell may enter G₀. |
| G₂ checkpoint | End of G₂, before mitosis | Has all the DNA been replicated correctly, without damage? |
| M checkpoint (spindle checkpoint) | During mitosis, before anaphase | Are all chromosomes properly attached to spindle fibers? Anaphase waits until they are. |
Cyclins and CDKs
Cyclin-dependent kinases (CDKs) are protein kinases (4.2): they drive the cycle forward by phosphorylating target proteins. A CDK is present in the cell all the time, but it's only active when it's bound to a protein called a cyclin. That's where the name comes from.
Cyclin levels rise and fall in a regular pattern. A cyclin builds up during part of the cycle, binds its CDK and activates it. The active cyclin-CDK complex phosphorylates proteins that move the cell to the next stage. Then the cyclin is destroyed, the CDK switches off, and that stage ends. Picture a graph of the cycle: CDK amount is a flat line, while cyclin amount climbs and then drops sharply, over and over, with CDK activity following the cyclin peaks.
One cyclin-CDK complex, sometimes called MPF (maturation- or M-phase-promoting factor), triggers the cell's entry into mitosis. You don't need to know specific cyclin-CDK pairs or the names of specific growth factors.
Outside signals
Cells also respond to signals from other cells (4.1). Growth factors are signal molecules that bind receptors and start a pathway that pushes the cell past the G₁ checkpoint. Normal animal cells in a dish also stop dividing when they become crowded and touch their neighbors, which is called density-dependent inhibition, and most need to be attached to a surface to divide.
When control fails: cancer and apoptosis
Cancer is uncontrolled cell division. It usually results from mutations in genes that regulate the cycle. Proto-oncogenes are normal genes that promote division, such as genes for growth factor receptors or relay proteins. A mutation can turn one into an oncogene that's stuck on, like a gas pedal held down. Tumor suppressor genes normally slow or stop division, or trigger apoptosis. Mutations that inactivate them are like cutting the brake lines.
A key tumor suppressor protein is p53. When DNA is damaged, p53 halts the cycle at the G₁ checkpoint so the DNA can be repaired. If the damage is too severe, it triggers apoptosis. Without working p53, damaged cells keep dividing and pile up more mutations. Cancer usually needs several mutations, both oncogenes and broken tumor suppressors, which is one reason cancer risk rises with age.
Apoptosis is the other possible outcome of a disruption. A cell that fails a checkpoint and can't fix the problem is usually destroyed in an orderly way, which protects the organism.
Worked examples
Try each one yourself first, then open the solution.
- Example 1Calculator allowed
Testing a treatment with chi-square
Researchers test whether a chemical increases cell division in root tips. In untreated (control) root tips, 10% of cells are in mitosis. In treated root tips, a count of 200 cells finds 50 in mitosis and 150 in interphase. Use a chi-square test with the control proportions as the expected values to decide whether the treatment changed the proportion of dividing cells (p = 0.05).
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- Step 1: Null hypothesis: the treatment has no effect, so treated root tips should have the same proportion of dividing cells as the control (10% mitosis, 90% interphase).
- Step 2: Expected values for 200 cells: mitosis = 0.10 × 200 = 20; interphase = 0.90 × 200 = 180.
- Step 3: χ² = Σ (o − e)²/e = (50 − 20)²/20 + (150 − 180)²/180 = 900/20 + 900/180 = 45 + 5 = 50.
- Step 4: Degrees of freedom = number of categories − 1 = 2 − 1 = 1. The critical value at p = 0.05 with 1 degree of freedom is 3.84.
- Step 5: 50 > 3.84, so reject the null hypothesis. The difference is too large to be explained by chance alone.
Answer: χ² = 50 with 1 degree of freedom, far above 3.84, so reject the null hypothesis: the treatment significantly increased the proportion of cells in mitosis.
- Example 2
Reading a cyclin graph
In a dividing cell, the amount of a particular cyclin rises steadily during interphase, peaks just before mitosis, then drops sharply during mitosis. The amount of its CDK stays the same throughout. Researchers make a version of this cyclin that can't be destroyed. Predict the effect on the cell.
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- Step 1: Recall the rule: the CDK is active only when bound to cyclin.
- Step 2: Normally, the cyclin peak activates the CDK and pushes the cell into mitosis, and destroying the cyclin switches the CDK off so the cell can finish mitosis and divide.
- Step 3: With a cyclin that can't be destroyed, the CDK stays active.
- Step 4: The cell enters mitosis but can't switch off the 'mitosis' signal, so it has trouble finishing mitosis and getting back into interphase.
Answer: The CDK stays active, so the cell can enter mitosis but gets stuck, unable to complete mitosis and return to interphase.
- Example 3
Which kind of mutation? (classic trap)
A student says: 'Cancer happens when a mutation turns on a gene that stops cell division.' Identify the error and rewrite the statement.
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- Step 1: Genes that stop division are tumor suppressor genes. Turning them on would slow division, not cause cancer.
- Step 2: Cancer comes from losing that brake: mutations that inactivate tumor suppressor genes (like the gene for p53).
- Step 3: Cancer can also come from mutations that turn a proto-oncogene, a gene that promotes division, into an always-on oncogene.
- Step 4: Usually both kinds of mutation accumulate before a cell becomes cancerous.
Answer: Cancer results from mutations that inactivate tumor suppressor genes (which normally stop division) and/or mutations that turn proto-oncogenes (which promote division) into overactive oncogenes.
Common mistakes
- Saying CDK levels rise and fall. CDK amounts stay fairly constant; cyclin levels cycle, and CDK activity follows the cyclin.
- Mixing up proto-oncogenes and tumor suppressor genes. Proto-oncogenes promote division (gas pedal); tumor suppressors restrain it (brakes).
- Saying a failed checkpoint always means cancer. Often the cell repairs the problem or undergoes apoptosis.
- Writing the null hypothesis as 'the treatment increases division.' The null says there's no effect; the data either reject it or fail to reject it.
On the exam
- Expect graphs of cyclin, CDK activity or DNA content over the cycle, and questions that ask what happens when one control fails.
- Mitosis data from root-tip experiments are often analyzed with chi-square. State the null hypothesis, show expected values, compare χ² to the critical value and conclude.
Connected topics
Videos
Check yourself
4 questions on 4.6 Regulation of Cell Cycle. Pick an answer to see if you got it, and why.
| Stage | Cyclin level (relative) | CDK level (relative) | CDK activity (relative) |
|---|---|---|---|
| Early G₁ | 5 | 100 | 2 |
| S | 35 | 100 | 20 |
| G₂ | 80 | 100 | 60 |
| Start of mitosis | 100 | 100 | 95 |
| End of mitosis | 5 | 100 | 3 |
Experimental data: levels of one cyclin and its partner CDK, measured in a population of cells moving through the cell cycle together
Which conclusion is best supported by the data?
A mutation makes this CDK active at all times, even when cyclin levels are low. Which of the following is the most likely result?
After being exposed to radiation, a cell with damaged DNA stops in G₂ and does not enter mitosis until the damage is repaired. Which of the following best explains the benefit of this pause?
A protein normally stops the cell cycle when DNA is damaged. Which of the following is the most likely consequence of a mutation that inactivates this protein?
0 of 4 answered