Oncogenes and Tumour Suppressor Genes Revision Notes | A Level AQA Biology

1. Why Cell Division Needs a Control System

Every second, billions of cells in your body divide, repair, and replace themselves. That process works because it is tightly regulated — accelerator genes push division forward, and brake genes hold it back. When that balance breaks down, the result can be a tumour.

This lesson unpacks the two key players in that regulatory system: oncogenes and tumour suppressor genes. Understanding how each one fails — and why abnormal methylation makes things worse — is exactly what AQA examiners test at A-level.

2. Proto-oncogenes: The Accelerators of Cell Division

Picture the cell cycle as a car journey. Proto-oncogenes are the accelerator pedal — they encode proteins such as growth factors, growth factor receptors, and transcription factors that stimulate the cell to divide. In a healthy cell, they are switched on only when division is needed, then switched off again.

When a proto-oncogene undergoes a mutation — a base substitution, gene amplification, or chromosomal translocation — it can become permanently switched on. At that point it is reclassified as an oncogene. The protein product is either overproduced or constitutively active, meaning it signals for cell division continuously, regardless of whether the cell actually needs to divide.

A classic analogy: the accelerator pedal is now jammed to the floor. The cell cannot stop dividing, and daughter cells inherit the same faulty gene, compounding the problem with every generation.

3. Tumour Suppressor Genes: The Brakes on Cell Division

Now picture the other side of the control system. Tumour suppressor genes encode proteins that act as brakes — they inhibit progression through the cell cycle, trigger apoptosis (programmed cell death) in damaged cells, or oversee DNA repair. The most studied example is TP53, which encodes the p53 protein; p53 detects DNA damage and either halts the cell cycle for repair or initiates apoptosis if the damage is irreparable.

Tumour suppressor genes follow what is known as the two-hit hypothesis: because most cells carry two alleles, both copies must be inactivated before the braking effect is lost. A single mutation in one allele is usually insufficient on its own — the remaining functional allele compensates. It is only when the second allele is also inactivated (by a second mutation, deletion, or epigenetic silencing) that control is fully lost.

With no functional tumour suppressor protein, damaged or abnormal cells that would normally be destroyed are instead allowed to survive and continue dividing. This is a critical step on the road to tumour formation.

4. Abnormal Methylation and Its Role in Tumour Development

So far, we have focused on mutations that change the DNA sequence itself. There is a second, equally important route to cancer: epigenetic changes — alterations to gene expression that do not involve changes to the base sequence. The key epigenetic mechanism here is DNA methylation.

Methylation involves the addition of a methyl group ($-CH_3$) to cytosine bases, typically at CpG sites (regions where cytosine is followed by guanine). When the promoter region of a gene becomes heavily methylated, transcription factors cannot bind effectively, and the gene is silenced — its protein product is no longer made.

In a normal cell, methylation patterns are carefully maintained. In cancer cells, those patterns go wrong in two distinct directions, and both directions contribute to tumour development.

Notice the asymmetry: tumour suppressor genes are silenced by too much methylation at their promoters (hypermethylation), while proto-oncogenes are activated by too little methylation (hypomethylation). Both outcomes push the cell towards uncontrolled division, but through opposite epigenetic mechanisms.

5. How These Changes Combine to Produce a Tumour

Tumour development is rarely caused by a single event. It is a multi-step process in which mutations and epigenetic changes accumulate over time. Think of it as a series of safety systems failing one by one.

Worked example: Tracing the Pathway from Normal Cell to Tumour

Explain, in sequence, how a normal cell can develop into a tumour cell through changes to oncogenes and tumour suppressor genes.

1. Normal cell: proto-oncogenes are expressed only when needed; tumour suppressor genes are active and producing functional proteins. — This is the baseline — both the accelerator and the brake are working correctly.
2. A mutation (e.g. base substitution) or hypomethylation converts a proto-oncogene into an oncogene. The oncogene product continuously stimulates cell division. — The accelerator is now stuck. However, tumour suppressor genes may still partially compensate at this stage.
3. A mutation or hypermethylation of the promoter silences one allele of a tumour suppressor gene. The remaining allele still produces some functional protein. — The brake is weakened but not yet fully lost — the two-hit hypothesis means one functional allele can still provide some control.
4. The second allele is also mutated or epigenetically silenced. No functional tumour suppressor protein is produced. — The brake is now completely gone. The cell divides continuously and cannot be stopped by normal regulatory signals.
5. Uncontrolled cell division produces a mass of cells — a tumour. Because daughter cells inherit the same genetic and epigenetic changes, the abnormal phenotype is perpetuated. — Each daughter cell carries the same faulty oncogene and non-functional tumour suppressor genes, so the tumour grows.

Answer: Tumour formation results from the accumulation of changes — oncogene activation (by mutation or hypomethylation) combined with inactivation of both alleles of tumour suppressor genes (by mutation or hypermethylation) — that together remove all normal restraints on cell division.

A key point for exam answers: neither oncogene activation nor tumour suppressor gene inactivation alone is usually sufficient. Cancer typically requires multiple changes accumulating in the same cell lineage over time. This is why cancer risk increases with age — there has been more time for errors to accumulate.

6. Comparing Oncogenes and Tumour Suppressor Genes

Examiners frequently ask you to compare these two gene types. The table below consolidates the key contrasts — use it as a revision anchor before tackling exam questions that use the command word 'compare'.

7. Exam Technique: Writing High-Quality Answers

The concepts in this lesson appear across several AQA command words. Here is how to translate your understanding into mark-winning responses.