Tumour Suppressor Genes (FS Week 8) Flashcards
What is the difference between targeted therapies and chemotherapy
targeted therapy cancer drugs block the growth and spread of cancer by interfering with specific molecules that are involved in growth, progression and spread of cancer
Chemotherapy is a range of anti-cancer drugs that are used to prolong life and reduce symptoms
What is a tumour suppressor gene
they encode proteins that maintain the checkpoints in the cell cycle and control genome stability
How do TSGs inhibit proliferation and replication of damaged cells
- repair damaged DNA (MLH1, BRCA1,2)
- apoptosis (TP53)
What is the knudson two-hit hypothesis
that most TSGs need both alleles to be inactivated either through mutations or epigenetic silencing to cause a phenotypic change
Why do heritable cancers develop
they develop after there is an additional loss of a normal functioning allele there is a loss of heterozygosity (one allele was already mutated for which they inherited)
Name the 3 tumour suppressor genes
- BRCA1,2
- TP53
- RB1
What is the function of a TSG
they are oncogene antagonists
they block the proliferation and cell cycle
DNA repair
induce apoptosis
What are the pathways of BRCA1,2
- removal of DNA lesions
- tolerance to DNA damage
- protection from errors of incorporation made during DNA replication
What cancers are associated with BRCA mutations
- breast
- ovarian
- male breast cancer
- prostate
- pancreatic
What is meant by ‘synthetic leathality’
a type of genetic interaction where the combination of two genetic events result in cell death/death of an organism
What is a PARP enzyme
a critical enzyme involved in DNA repair
Describe an example of synthetic leathility
PARP inhibitors prevent PARP function of repairing single strand DNA. Cells that have a mutated BRCA1,2 gene as well means that double strands of DNA is not repaired - this can lead to cell death
What is TP53
is a gene that instructs cells to produce tumour protein P53 which acts as a tumour suppressor so cells don’t divide in an uncontrolled manner
What regulates P53 in a negative feedback loop
MDM2 regulates P53 levels which induces MDM2 levels (negative feedback)
by inhibiting transcriptional activity and trigger degradation
What is Li-Fraumani syndrome
it is a hereditary genetic condition caused by a mutation in TP53 which is a genetic blueprint for p53
