D2.1.16 Consequences of mutations in genes that control the cell cycle (HL) Notes

Consequences of Mutations in Genes That Control the Cell Cycle

1. Imagine you're driving a car with two critical controls: an accelerator to move forward and brakes to stop.
2. Now, what if the accelerator gets stuck, or the brakes fail?
3. The car would speed out of control, leading to a crash.
4. This mirrors what happens in cells when mutations disrupt the genes controlling the cell cycle, leading to uncontrolled cell division and, potentially, cancer.

Proto-oncogenes and Oncogenes Are The Accelerators of The Cell Cycle

1. When these genes mutate, they become oncogenes, which push the cell to divide uncontrollably, even when it shouldn’t.

How Do Proto-oncogenes Become Oncogenes?

1. Point Mutations: A single base change in the DNA sequence can make the protein product hyperactive.
2. Gene Amplification: Multiple copies of the proto-oncogene lead to excessive protein production.
3. Chromosomal Rearrangements: Parts of chromosomes break and reattach incorrectly, placing proto-oncogenes under the control of highly active promoters.

Tumour Suppressor Genes Are The Brakes of The Cell Cycle

1. Tumour suppressor genes act as the brakes of the cell cycle, ensuring cells don’t divide too rapidly or inappropriately.
2. When these genes are mutated, the brakes fail, allowing uncontrolled division.

Key Functions of Tumour Suppressor Genes

1. Cell Cycle Regulation: Proteins like $p53$ halt the cycle if DNA is damaged, allowing time for repair.
2. DNA Repair: Genes like $BRCA1$ fix DNA errors during replication.
3. Apoptosis: If damage is irreparable, these genes trigger programmed cell death to prevent faulty cells from surviving.

What Happens When Tumour Suppressor Genes Fail?

1. Unchecked Division: Cells bypass checkpoints and continue dividing.
2. Accumulation of Mutations: Without DNA repair, errors multiply.
3. Avoidance of Apoptosis: Damaged cells survive and proliferate.

Uncontrolled Cell Division Leads to to Tumours

1. Mutations in proto-oncogenes and tumour suppressor genes disrupt the balance of the cell cycle, leading to:
2. Excessive Cell Proliferation: Cells divide rapidly, forming a mass called a tumour.
3. Loss of Differentiation: Tumour cells often lose their specialized functions.
4. Invasion and Metastasis: Malignant tumours spread to other tissues, causing cancer.

Why Multiple Mutations Are Needed

1. A single mutation is rarely enough to cause cancer.
2. It usually takes multiple mutations in different genes to fully disrupt the cell cycle and lead to malignancy.

Steps in Cancer Development

1. Initiation: A mutation in a proto-oncogene or tumour suppressor gene.
2. Promotion: Additional mutations increase cell division.
3. Progression: Cells acquire the ability to invade other tissues and metastasize.

The Role of Mutagens

1. Mutagens are agents that increase the likelihood of mutations.
2. They can be:
   1. Chemical: Substances like tobacco smoke or asbestos.
   2. Radiation: High-energy radiation such as X-rays or UV light.