Topic 4.6 Notes – Regulation of Cell Cycle

1. The Cell Cycle and Why It Must Be Controlled

The cell cycle is the ordered sequence of growth and division in a cell.

It has two major parts:

• Interphase
  • G1 → cell grows, performs normal functions
  • S → DNA is replicated
  • G2 → cell prepares for mitosis
• M phase → mitosis + cytokinesis, producing two daughter cells

The diagram below shows how these phases fit together in a continuous cycle.

Overview of the eukaryotic cell cycle

Every time a cell divides, two things must go right:

• DNA must be copied accurately.
• Each daughter cell must receive one complete set of chromosomes.

If damaged DNA is copied or chromosomes are divided unevenly, mutations accumulate. In a multicellular organism, that can disrupt tissues or lead to tumors. So the cycle is not automatic. It is regulated.

This regulation happens at checkpoints.

2. The Three Major Cell Cycle Checkpoints

Checkpoints are internal control systems. They ask specific questions before allowing the cell to move forward.

G1 Checkpoint (Restriction Point)

This is the most important checkpoint.

The question here is simple: Should this cell divide?

The cell checks:

• Is the cell large enough?
• Are nutrients available?
• Are growth signals present?
• Is the DNA undamaged?

Possible outcomes:

• ✔️ Move into S phase
• ⏸ Pause to repair DNA
• ➡ Enter G0 (non-dividing state; many specialized cells stay here)
• ❌ Trigger apoptosis if damage is severe

Most cells that become cancerous have problems at this checkpoint. On exams, if you see a mutation that causes cells to divide without growth signals, think G1 checkpoint failure.

G2 Checkpoint

Now the DNA has already been replicated.

The question becomes: Was replication completed correctly?

The cell checks:

• Was all DNA copied?
• Is there post-replication DNA damage?

If errors are detected, repair mechanisms activate. If repair fails, apoptosis can be triggered.

This prevents a cell from entering mitosis with duplicated but damaged chromosomes.

M Checkpoint (Spindle Checkpoint)

This occurs during metaphase of mitosis.

The key question: Are all chromosomes properly attached to spindle fibers?

The cell checks:

• Are kinetochores attached to spindle microtubules?
• Are chromosomes aligned at the metaphase plate?

In the metaphase stage shown below, chromosomes line up at the cell’s equator and each sister chromatid is attached to spindle fibers from opposite poles.

Stages of mitosis, highlighting metaphase spindle attachment

If even one chromosome is not attached correctly, the cell pauses. This prevents aneuploidy (incorrect chromosome number), which shows up often in data-based AP questions involving chromosomal abnormalities.

3. How Cyclins and CDKs Control the Cell Cycle

Checkpoints don’t act randomly. They’re controlled by protein interactions.

Cyclins

• Regulatory proteins
• Concentrations rise and fall during the cycle
• Synthesized and degraded at specific times

Their fluctuating levels act like timing signals.

Cyclin-Dependent Kinases (CDKs)

• Enzymes present at fairly constant levels
• Inactive alone
• Activated only when bound to a cyclin

Cyclin-CDK Complexes

When a cyclin binds to a CDK:

• The CDK changes shape
• Becomes active
• Phosphorylates target proteins
• Pushes the cell past a checkpoint

Key ideas you should connect:

• Different cyclins are active at different phases.
• Cyclins are degraded after use, turning off the signal.
• This makes progression directional. The cell cannot go backward.

The AP does not require memorizing specific cyclin names. What matters is understanding that fluctuating cyclin levels + constant CDKs = controlled progression.

If a graph shows cyclin concentration rising before mitosis and then sharply dropping, that drop represents degradation after checkpoint passage.

4. What Happens When Cell Cycle Regulation Fails

Cancer

Cancer results from loss of checkpoint control.

Common outcomes of mutations:

• Cells bypass the G1 checkpoint
• DNA damage is not repaired
• Cyclin-CDK activity becomes continuous
• Cells divide without growth signals

Cancer cells often:

• Ignore stop signals
• Avoid apoptosis
• Divide excessively, forming tumors

In experimental scenarios, if a gene mutation leads to constant CDK activation, expect uncontrolled proliferation.

Apoptosis

Apoptosis is programmed cell death.

It occurs when:

• DNA damage is irreparable
• Checkpoints detect major errors
• Developmental signals require cell removal

Its role:

• Eliminates damaged cells
• Prevents mutation spread
• Maintains tissue health

Think of apoptosis as the backup safety system. When repair fails, the cell self-destructs to protect the organism.