1.5 Protein control of 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.
• 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
• 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.
• 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 cyclindependent kinases (CDKs). Active cyclinCDK 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 tumourpromoting oncogene
• 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 tumoursuppressor 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