explain how uncontrolled cell division can result in the formation of a tumour

Replication and Division of Nuclei and Cells

Structure of a Chromosome (Syllabus 5.1)

• DNA double helix wrapped around histone proteins to form nucleosomes – the classic “beads‑on‑a‑string”.
• Two identical copies of each chromosome are held together as sister chromatids.
• Centromere – the constriction where spindle fibres attach via kinetochores.
• Telomeres – specialised DNA‑protein caps at the ends of each chromatid that protect the chromosome and prevent loss of genes during DNA replication.

Why Mitosis Is Important (Syllabus 5.1)

Mitosis provides a controlled way of producing new cells. It is essential for:

• Growth – increasing the size of an organism.
• Repair and replacement – restoring damaged tissues (e.g., skin, liver).
• Stem‑cell function – stem cells divide by mitosis to supply differentiated cells for continual tissue turnover.
• Asexual reproduction – many plants, fungi and some animals generate offspring directly through mitotic division (e.g., hydra, certain fungi).

The Mitotic Cell Cycle (Syllabus 5.1)

The cycle consists of interphase (growth and DNA synthesis), mitosis (nuclear division) and cytokinesis (cytoplasmic division).

Interphase

1. G1 phase – cell growth: synthesis of proteins, organelles and ribosomes; cell prepares for DNA replication.
2. S phase – DNA synthesis: each chromosome is duplicated, producing sister chromatids.
3. G2 phase – preparation for mitosis: further growth, production of mitotic spindle components, and checkpoint checks for DNA integrity.

Mitosis (M‑phase)

Division of the nucleus through four ordered stages.

Cytokinesis

• Animal cells: a cleavage furrow forms by contraction of an actin‑myosin contractile ring, pinching the cell into two daughters.
• Plant cells: a cell plate develops at the centre of the cell, eventually becoming a new cell wall.

Behaviour of Chromosomes & Nuclear Envelope During Mitosis (Syllabus 5.2)

Stage	Key Events (including chromosome & nuclear‑envelope dynamics)
Prophase	Chromatin condenses into visible chromosomes (each with two sister chromatids). Centrosomes migrate to opposite poles; spindle fibres begin to form. The nuclear envelope starts to break down (disassembly of nuclear pores).
Metaphase	Chromosomes line up along the metaphase plate (equatorial plane). Each sister chromatid’s kinetochore attaches to spindle fibres from opposite poles. The nuclear envelope is completely absent.
Anaphase	Sister chromatids separate at the centromere and are pulled toward opposite poles by shortening spindle fibres. The cell elongates as polar microtubules push the poles apart.
Telophase	Chromatids reach the poles and begin to de‑condense into chromatin. New nuclear envelopes re‑form around each set of chromosomes. Spindle fibres disassemble.

Tip: Interpreting Photomicrographs & Diagrams (Syllabus 5.2)

Control of the Cell Cycle (Syllabus 5.2)

1. Cyclins – proteins whose levels rise and fall each cycle, providing the timing cue.
2. Cyclin‑dependent kinases (CDKs) – enzymes activated by binding cyclins; they phosphorylate target proteins to drive the cycle forward.
3. Checkpoints – surveillance mechanisms (G1, G2, spindle) that ensure the cell only progresses when conditions are suitable.

Uncontrolled Cell Division and Tumour Formation (Syllabus 5.2)

What Is a Tumour?

An abnormal mass of tissue produced by excessive cell proliferation. Tumours are classified as:

• Benign – localized, non‑invasive, usually harmless.
• Malignant – invasive, capable of metastasis, and potentially life‑threatening.

How Loss of Regulation Leads to Uncontrolled Division

Normal regulation ensures cells divide only when required. Disruption can occur through:

• Mutations in genes that encode cyclins or CDKs.
• Damage to tumour‑suppressor genes (e.g., p53, RB) that normally halt the cycle or trigger apoptosis.
• Activation of oncogenes (e.g., RAS, MYC) that drive the cell cycle forward.
• Failure of checkpoint mechanisms, allowing cells with DNA damage to continue dividing.

Sequence of Events Leading to a Tumour

1. DNA damage occurs (e.g., from UV radiation, chemicals, viruses).
2. Repair mechanisms are defective or become overwhelmed.
3. Mutations accumulate in genes that control the cell cycle.
4. Checkpoints become ineffective; the cell proceeds through G1/S or G2/M despite abnormalities.
5. Uncontrolled proliferation creates a clonal population of abnormal cells.
6. Further mutations confer additional abilities such as tissue invasion and angiogenesis, converting a benign growth into a malignant tumour.

Key Molecular Change – The p53 Pathway (Illustrative Example)

Normal response to DNA damage:

$$\text{DNA damage} \;\xrightarrow{\text{activate}} \; p53 \;\xrightarrow{\text{transcribe}} \; p21 \;\xrightarrow{\text{inhibit}} \; \text{CDK–cyclin complexes} \;\Rightarrow\; \text{Cell‑cycle arrest}$$

If the TP53 gene is mutated, p53 cannot be activated, p21 is not produced, CDK–cyclin activity remains unchecked, and the cell proceeds through the cycle with damaged DNA, increasing tumour risk.

Comparative Table: Normal vs. Uncontrolled Division

Feature	Normal Cell Division	Uncontrolled (Tumour) Division
Growth signals	Require external mitogens	Autonomous signalling or constitutive pathway activation
Checkpoint integrity	Functional G1, G2, spindle checkpoints	Checkpoint proteins mutated or down‑regulated
DNA integrity	Repair mechanisms active; apoptosis if damage severe	Defective repair; apoptosis evaded
Cell‑cycle duration	Regulated, variable depending on tissue	Shortened; rapid progression through phases
Outcome	Controlled tissue growth and replacement	Mass formation; possible invasion and metastasis

Summary

Uncontrolled cell division arises when the tightly regulated network of cyclins, CDKs, checkpoints, and tumour‑suppressor genes is disrupted. The loss of these controls permits cells with damaged DNA to proliferate, forming a tumour. Understanding these mechanisms is fundamental to the study of cancer biology and the development of targeted therapies.