DNA repair and cancer Flashcards
Why is DNA integrity important
Don’t want mutations
mutation can lead to cancer
want to pass on the correct DNA to the next generation
Exogenous DNA damage
Ionising radiation alkylating agents mutagenic chemicals anti-cancer drugs free radicals
Endogenous sources of DNA damage
Replication error
free radicals
Types of DNA damage
Apurinic site deamination mismatch pyrimidine dimers double-stranded and single-stranded DNA breaks intercalating agents interstand crosslink bulky adults
apurinic site
Location in DNA that has neither a purine or a pyrimidine base
Deamination
C->U
Pyrimidine dimer
UV likeability links adjacent T orC
Bulky adducts
Ads on a bulky chemical to bases
DNA replication stress
Inefficient replication that leads to replications fork slowing, stalling and/breakage
What can cause DNA replication stress
Replication machinery defects
replication fork progression hindrance
defects in response pathways
Replication for progression hindrance examples
Pyrimidine dimers repetitive DNA DNA secondary structure fragile sites on DNA transcription bubble ahead
Issues with repetitive DNA
Can cause replication fork slippage, depending on the Strand it occurs can result in addition or loss of nucleotides
Trinucleotide repeat disorders name one
Huntington’s
Describe Huntington’s disease
HTT gene CAG repeat- results in poly glutamate repeats normal individual has 6 to 39 repeat disease 35 221 repeats these two neuron derogation
DNA damage response has three different outcomes
Senescence
proliferation
apoptosis
Base excision repair
Useful single-stranded break, U or a basic site
Nucleotide excision repair
Pyrimidine dimers, moves larger region
Mismatch repair
With little region
How to repair double-stranded breaks
Non-homologous end joining
homologous director prepare
Which stage of the cell cycle would use homologous recombination the most
Synthesis, as has a template strand to use
Describe nonhomologous end joining
KU70/80 protects’s
DNA PKcs removes damaged ends
broken and ligated together
Describe the process of homologous recombination
Resection- XO nucleus has cut DNA to make single-stranded DNA which is commentary sister chromatid
single strands can now invade opposite chromosome
D loop formation
Holliday junction migration
result either non-crossover product or crossover product due to the way strands are cut
Intra tumour heterogeneity
Many sub clones in tumour
Synthetically full strategies being used for BRAC1/2
PARP
use information on pathways and genes which are mutated to our advantage we know the cancer cells can handle double strand breaks very well therefore to our advantage
