4: Mechanisms Of Oncogene Activation, Function, And Relation To Cancer I Flashcards
(51 cards)
Why does cancer incidence increase with age?
Older people have undergone more divisions of their cells, therefore there is an increased chance of mutation during those divisions
What are mutations
Permanent changes to the DNA sequence of a gene
What are the 6 forms of mutations
- Single nucleotide variations
- Insertions/deletions
- Transolocations
- Aneuploidy
- Microsatellite instability
- Gene amplification
What is a single nucleotide mutation
A substitution of he base at an individual nucleotide
Eg CTG > CAG
What are insertions/deletions
The gain/loss of one or more nucleotides
What are translocations
The rearrangement of non-homologous chromosomes
(DNA of chromosomes switch)
What is Aneuploidy
The gain/loss of whole chromosomes
What is microsatellite instability?
Variation in short repeats found within the genome.
What is gene amplification
Many copies of the section containing the gene exist
What is a missense mutation
1 amino acid is changed in the point
What causes a nonsense mutation?
Where the mutated gene codes for a stop codon.
What is a frame shift mutation
Where the removal/addition of a base pair changes all amino acids after the mutation, the shift of the reading frame
What types of mutation often causes a loss of function?
Nonsense and frameshift
What type of mutation is likely to cause a gain of function?
Missense
What is a silent change in the coding region?
Where a point mutation changes a base pair, but the codon translates into the same amino acid.
This is due to the genetic code being degenerate.
Can silent change mutations make a difference to the formation of its protein?
A silent change will still produce the same amino acid, so the structure of the protein produced remains the same.
However, the tRNAs required for the different codons may vary in abundance, so rate of translation may be affected.
Oncogenes are typically activated, therefore if point mutations occur, what sort of mutation are they likely to be?
Missense
(Gain of function)
What are the 3 common isoforms of Ras?
K-Ras
N-Ras
H-Ras
What is G(N)EF and what does it do?
Guanine-nucleotide exchange factor
Promotes the release of GDP from Ras, and from the Ras catalytic pocket. This means the relative abundance of intracellular GTP compared to GDP ensures the binding of GTP to Ras
Switches Ras on
What are GAPs and what do they do?
GTPase-activating proteins
Promotes GTP hydrolysis. They accelerate the hydrolysis of GTP, therefore are negative regulators of Ras functions.
Which regulators promote and demote the functions of Ras?
Promote: GEF (Guanine-nucleotide exchange factors)
Demote: GAP (GTPase activating proteins)
Outline the normal Ras signalling.
- Inactive Ras is bound to GDP.
- Guanine-nucleotide Exchange Factors promote the preferential binding of GTP to Ras, instead of GDP.
- Ras is activated
- Downstream signalling pathways of Ras are activated
- GTPase activating proteins promote the hydrolysis of GTP, meaning Ras binds to GDP, inactivating Ras and its functions.
Outline oncogenic Ras signalling
GTPase is unable to bind to the Ras-GTP.
Ras remains in its active state, bound to GTP.
The cell loses its ability to regulate the Ras signalling pathways.
What can ERK activation lead to?
- Increased DNA synthesis
- Increased cell proliferation
