5. Protein control of cell division

Question 1

What is the cytoskeleton?

Answer 1

• The cytoskeleton gives mechanical support and shape to cells.
• It consists of different protein structures including microtubules, which are found in all eukaryotic cells.
• Cell division requires remodelling of the cytoskeleton.

Question 2

What are microtubules?

Answer 2

• Microtubules are hollow, straight cylinders composed of proteins called tubulins.
• They control the movement of membrane-bound organelles and chromosomes.
• The formation and breakdown of microtubules involves polymerisation (growth of the microtubule) and depolymerisation (shrinkage of the microtubule) of tubulin.
• Microtubules form the spindle fibres that are active during cell division.

Question 3

What is the cell cycle?

Answer 3

• Cell division allows organisms to grow and develop, to replace dead cells and repair tissue.
  The whole cycle can be divided up into two parts:
• Interphase.
• The mitotic (M) phase.

Question 4

What is interphase?

Answer 4

• During interphase, protein synthesis takes place, cytoplasmic organelles are synthesised, the cell grows and replicates its chromosomes.
  Interphase is divided into three sub-phases:
  1. G1 is the first ‘growth’ phase; it is a growth period where proteins and organelles are synthesised.
  2. During S phase the DNA is replicated in preparation for mitosis.
  3. The final phase is G2 (the second ‘growth’ phase); this is another growth period during which proteins and organelles are synthesised.

Question 5

What is mitosis?

Answer 5

At the end of G2, cells enter the mitotic phase (M), which is divided up into two stages.
1. Mitosis - when the nucleus and its contents divide. Mitosis consists of prophase, metaphase, anaphase and telophase.
2. Cytokinesis - the separation of the cytoplasm into daughter cells.

Question 6

How is the cell cycle regulated?

Answer 6

• Progression through the cell cycle is controlled by checkpoints. This is where stop and start signals regulate the cycle.
• Checkpoints are mechanisms within the cell that assess the condition of the cell during the cell cycle and halt progression to the next phase until certain requirements are met.
• The cell cycle must be controlled to ensure that events in the cell cycle proceed in the correct order and that each event is completed before the next starts.

Question 7

Describe the role of cyclin proteins in regulating the cell cycle.

Answer 7

• Cyclin proteins that accumulate during cell growth are involved in regulating the cell cycle.
• Cyclins combine with and activate cyclin-dependent kinases (CDKs).
• Active CDK complexes phosphorylate proteins that regulate progression through the cycle.
• If a sufficient threshold of phosphorylation is reached, the cell cycle moves on to the next stage.
• If an insufficient threshold is reached, the cell is held at a checkpoint.

Question 8

Describe the G1 checkpoint.

Answer 8

1. At the G1 checkpoint, retinoblastoma protein (Rb) acts as a tumour suppressor by inhibiting the transcription of genes that code for proteins needed for DNA replication.
2. The non-phosphorylated form of Rb restricts progression from G1 phase into S phase by binding to a transcription factor, therefore preventing transcription of certain genes required for S phase to begin; thus the cell remains in G1.
3. Phosphorylation by G1 cyclin-CDK inhibits the activity of Rb, meaning that it can no longer bind the transcription factor.
4. This allows transcription of the genes that code for proteins needed for DNA replication and allows cells to progress from G1 to S phase.

Question 9

Describe the G2 checkpoint.

Answer 9

• At the G2 checkpoint, the success of DNA replication and any damage to DNA is assessed.
• DNA damage triggers the activation of several proteins (eg. p53) that can stimulate DNA repair, arrest the cell cycle or cause cell death.

Question 10

Describe the M checkpoint.

Answer 10

• A metaphase checkpoint controls progression from metaphase to anaphase.
• At the metaphase checkpoint, progression is halted until the chromosomes are aligned correctly on the metaphase plate and attached to the spindle microtubules.
• This checkpoint ensures that each daughter cell receives the correct number of chromosomes.

Question 11

Why is controlling the cell cycle important?

Answer 11

• An uncontrolled reduction in the rate of the cell cycle may result in degenerative disease.
• An uncontrolled increase in the rate of the cell cycle may result in tumour formation.
• A proto-oncogene is a normal gene, usually involved in the control of cell growth or division, which can mutate to form a tumour-promoting oncogene.

Question 12

Describe apoptosis.

Answer 12

• Apoptosis is triggered by cell death signals that can be external or internal
• External death signal molecules bind to a surface receptor protein and trigger a protein cascade within the cytoplasm
• An internal death signal resulting from DNA damage causes activation of p53 tumour-suppressor protein.
• Both types of death signal result in the activation of caspases (types of protease enzyme) that cause the destruction of the cell.
• Cells may initiate apoptosis in the absence of growth factors.