Carla - TS genes and mutations Flashcards
What % of human cancers are caused by p53 mutations?
Between 50 and 60% of cancers
Between 50 and 6-% of human cancers are caused by p53 mutations, describe these mutations
90% of these mutations encode missense mutant proteins (change in amino acid arising from a point mutation)
These mutations span 190 different codons localised in the DNA binding domain of the gene and protein
What does the p53 protein actually do?
(3)
It binds to regulatory sites in the genome
Here it begins production of proteins that halt cell division until the damage is repaired
Or if damage is too severe, p53 initiates apoptosis and permanently removes the damage
What are the four outcomes of a mutation?
Wild type
Silent mutation
Missense mutation
Nonsense mutation
What is a wild type mutation?
There is no change in base pair
The mutation results in the same base pair
What is a silent mutation?
The change in base pair results in the same amino acid being produced
What is a nonsense mutation?
No amino acid produced -> stop codon produced
What is a missense mutation?
Different base pair resulting in a different amino acid
Write a note on retinoblastoma associated protein
(6)
First tumour suppressant protein
200,000 base pairs long
27 exons long
Loss of function often central step in cancer development
Responsible for a major G1 checkpoint, blocking S-phase entry and cell growth
Central regulator of the cell cycle
Write a note on p21
(4)
Its expression is induced by p53 following DNA damage detection
Protein = p21/CDKN1A
CDKI is an inhibitor of cyclin dependant kinase – stops cell cycle progression – inhibits cyclins found in S and GI phase
Mutant p53 or low p53 levels – you wont have p21 -> leads to oncogenesis
What is CDKI?
An inhibitor of cyclin dependant kinase inhibitor – stops cell cycle progression – inhibits cyclins found in S and GI phase
What does CDK1 inhibit?
S and G1 phase Cyclin dependant kinases
What induces the expression of p21?
p53 when it detects DNA damage
What happens to p21 when you have a mutant p53 or low p53 levels?
You will have low levels of p21
What is p21 also called?
Cyclin dependant kinase inhibitor 1
CDK interacting protein 1
