Lesson 8 of 9 / Mutation, cell division and cancer
When division controls fail
How do a damaged brake and a stuck growth signal differ?
In this lesson: Explain checkpoint regulation, p53 loss and ras activation.
About 7 min
The key ideaLoss of tumour-suppressor function removes restraint; gain of proto-oncogene function can provide persistent growth-promoting signals.
Track the mechanism
Loss of a restraint or gain of a growth signal?
Normal Ras signalling responds to growth cues and switches off. Normal p53 supports protective responses to DNA damage. Positive signals and protective restraints both contribute to regulated division.
The bar symbol represents restraint on progression; the broken bar represents loss of that protection. This is a regulatory comparison, not a literal map in which p53 directly binds Ras. Several cooperating changes usually contribute to cancer.
Explanation
Normal cells regulate progression through the cell cycle so that damaged DNA and incomplete division steps are not simply propagated. Tumour-suppressor genes encode products that restrain inappropriate proliferation or support protective responses. Loss of their function can remove these controls.
p53 is a tumour-suppressor protein involved in responses to DNA damage, including arrest that permits repair and, when appropriate, promotion of cell death. Loss of p53 function can allow damaged cells to continue dividing. A tumour suppressor is not a gene whose normal role is to cause tumours.
A proto-oncogene has a normal role in growth or survival signalling. A gain-of-function change can turn it into an oncogene. Ras is a signalling protein that normally switches between active and inactive states; an activating mutation can keep growth-promoting signalling on inappropriately.
These are different directions of functional change: reduced protective action versus increased growth-promoting action. Cancer usually requires accumulation of cooperating changes rather than one universal mutation. Describing regulation at this level is sufficient here; the syllabus does not require the detailed molecular architecture of every checkpoint.
Step by step
- 1
State the normal role
Begin with a protective control or growth signal.
- 2
State the mutation direction
Loss of function or gain of function.
- 3
Link to cell behaviour
Explain inappropriate survival or continued division.
Worked example
Work through the evidence
A mutant Ras cannot switch off its growth signal. Why is this a gain-of-function cancer mechanism?
One way to explain it
The growth-promoting activity persists when it should stop, adding inappropriate signalling rather than merely removing Ras from the cell.
Why this answer works
- Gain refers to abnormal functional activity, not necessarily more DNA copies.
- Contrast it with loss of p53-mediated restraint.
Is this true? "A proto-oncogene is already a harmful gene with no normal function."
Proto-oncogenes have normal cellular roles; particular activating changes make them oncogenic.