Tumour suppressor genes

• What are protooncogenes

  Genes that regulate cell proliferation.
• What are oncogenes

  A mutated protoncogene with a gain of function.
• How are oncogenes formed.

  • Translocation
  • Gene amplification
  • Point mutation within the controlled element
  • Point mutation within the gene
• Which methods of forming oncogenes results in a hyperactive protein

  Point mutation within the gene.
• Which methods of oncogene formation results in excess growth factors

  Translocation, Point mutation within the controlled element and gene amplification.
• what is the effect of translocation in a protooncogene

  Gene is moved to a new position and transcribed more frequently.
• What is the effect of gene amplification on a protooncogene

  More genes are replicated so more growth factor is produced.
• What is the effect of a point mutation within the control element of a gene.

  More efficient transcription.
• what is the effect of a point mutation within the gene.

  Growth factor is hyperactive or degradation resistant.
• Describe the signalling pathway for an oncogene

  • Protein kinase receptor is autophosphorylated when growth factor binds
  • Phosphorylation cascade
  • Tanscription factor is phosphorylated
  • Gene expression
• Name an example of a protooncogene

  Ras
• What type of mutation forms the Ras oncogene

  Point mutation
• Describe the signalling pathway for Ras

  1. Receptor is autophosphorylated
  2. Ras is activated by GTP
  3. Phosphorylation cascade
  4. Transcription factor
  5. Cyclins produced
• How does the Ras oncogene cause uncontrolled proliferation

  The Ras oncogene is permanently bound to GTP, and so is constantly activated. This causes excessive cyclin production which stimulates the cell cycle.
• What type of mutations cause oncogenes

  Dominant
• What type of mutations are tumour suppressor gene mutations

  Recessive
• What do tumour suppressor gene mutations do

  Inactivate proteins which inhibit the cell cycle.
• what do tumour suppressor genes do

  Inhibit cell division
• Give two examples of tumour suppressor genes

  P53 and Retinoblastoma protein.
• What is retinoblastoma

  Tumour of the retina
• What are the two forms of retinaoblastoma

  Familial and sporadic.
• What are the features of familial retinoblastoma

  Occurs in young children and forms tumours in both eyes. It is genetically passed from parents.
• What are the features of sporadic retinoblastoma

  It occurs later in life and usually affects just one eye. Caused by a mutation in both copies of the tumour suppressor gene.
• What does cell proliferation of the retina cause

  White appearance of eyes due to the tumour.
• Why is retinoblastoma recessive with a dominant inheritance pattern

  It first starts with inheritance from a carrier and then a somatic mutation.
• What causes the somatic mutation in retinoblastoma

  Mitotic recombination
• How does the retinoblastoma tumour suppressor work

  Retinoblastoma inhibits progression through the G1 checkpoint.
• How does the retinoblastoma mutated tumour suppressor cause cancer

  Inactivates pRb which results in a loss of the G1 checkpoint.
• What does the retinoblastoma produce

  pRb
• What is senescence

  A permanent non-replicative state.
• What is the main role of the p53 tumour suppressor

  
  

  Produces proteins which inhibit the cell cycle allowing for DNA repair.
• Which checkpoints does p53 work at

  G1 and G2
• Which protein does p53 increase expressio nof

  P21
• What does p21 do

  Inhibits Cyclin e and Cyclin dependent kinase 2 [SPF]. Prevents the cell from passing through the G1 checkpoint.
• What regulates DNA repair proteins

  p53
• What protein regulates apoptosis

  p53
• How do mutations in p53 cause cancer

  Allows the cell to replicate with damaged DNA.
• Describe how mitotic recombination contributes to retinoblastoma

  Mitotic recombination results in the inheritance of two mutant alleles.
• What is apoptosis

  Programmed cell death which does not cause an inflammatory response.
• What are the steps in apoptosis?

  1. p53 activates apoptosis due to DNA damage
  2. Cell shrinks and membrane blebs
  3. DNA is dissolved by enzymes
  4. Organelles are packaged in vesicles
  5. Macrophages phagocytose the apoptotic bodies