(a) The cytoskeleton and cell division

• The cytoskeleton gives mechanical support and shape to cells

• It consists of different protein structures including microtubules, which are found in all eukaryotic cells

  • Microtubules are hollow cylinders composed of the protein tubulin. 

  • They radiate from the microtubule organising centre (MTOC) or centrosome.

  • Knowledge of other cytoskeleton proteins is not required.

• Microtubules control the movement of membrane-bound organelles and chromosomes

• Cell division requires remodelling of the cytoskeleton

• Formation and breakdown of microtubules involves polymerisation and depolymerisation of tubulin

• Microtubules form the spindle fibres that are active during cell division

(b) The cell cycle

• The cell cycle consists of interphase and mitotic (M) phase

  • Interphase involves growth and DNA synthesis including G1, a growth phase; S phase, during which the DNA is replicated; and G2, a further growth phase.

• Mitotic phase involves mitosis and cytokinesis

  • In mitosis the chromosomal material is separated by the spindle microtubules. 

  • This is followed by cytokinesis, in which the cytoplasm is separated into two daughter cells.

• Mitosis consists of prophase, metaphase, anaphase and telophase

  • Prophase — DNA condenses into chromosomes each consisting of two sister chromatids. Nuclear membrane breaks down; spindle microtubules extend from the MTOC by polymerisation and attach to chromosomes via their kinetochores in the centromere region.

  • Metaphase — chromosomes are aligned at the metaphase plate (equator of the spindle).

  • Anaphase — as spindle microtubules shorten by depolymerisation, sister chromatids are separated, and the chromosomes are pulled to opposite poles.

  • Telophase — the chromosomes decondense and nuclear membranes are formed around them.

(c) Control of the cell cycle

• Progression through the cell cycle is controlled by checkpoints

  • 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.

• Cyclin proteins that accumulate during cell growth are involved in regulating the cell cycle

  • Cyclins combine with and activate cyclin-dependent kinases (CDKs). 

  • Active cyclin-CDK complexes phosphorylate proteins that regulate progression through the cycle. 

  • If sufficient phosphorylation is reached, progression occurs.

• 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

• Phosphorylation by G1 cyclin-CDK inhibits the retinoblastoma protein (Rb)

  • This allows transcription of the genes that code for proteins needed for DNA replication. Cells progress from G1 to S phase.

• At the G2 checkpoint, the success of DNA replication and any damage to DNA is assessed

• DNA damage triggers the activation of several proteins including p53 that can stimulate DNA repair, arrest the cell cycle or cause cell death

• 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.

• 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

(d) Control of programmed cell death (apoptosis)

• Apoptosis is triggered by cell death signals that can be external or internal

  • The production of death signal molecules from lymphocytes is an example of an external death signal. 

  • DNA damage is an example of an internal death signal.

• 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

• Apoptosis is essential during development of an organism to remove cells no longer required as development progresses or during metamorphosis

• Cells may initiate apoptosis in the absence of growth factors