DNA Repair And Cancer Flashcards
Name 5 exogenous sources that cause DNA damage
Ionising radiation Alkylating agents Mutagenic chemicals Anti-cancer drugs Free radicals
Name 2 endogenous sources of DNA damage
Replication errors
Free radicals
What is DNA replication stress?
Inefficient replication that leads to replication fork slowing, stalling and/or breakage
How are mismatches removed from DNA replications?
Removed by 3’ to 5’ DNA exonuclease
DNA polymerase then continues to replicate 5’ to 3’
What happens if the new strand is synthesised too slowly?
Newly synthesised strand loops out and one nucleotide is added to the new strand
What happens I the new strand is synthesised to fast?
The template strand loops out and one nucleotide is omitted on the new strand
Trinucleotide repeat disorders
Fork slippage leads to trinucleotide expansion
Can cause diseases such as Huntington’s, spinocerebellar ataxia, fragile X
What are the 5 possible ways a cell deals with replication stress?
DNA repair Transcription Apoptosis Cell cycle transitions Senescence (permanent cell cycle arrest)
What are the steps of DNA damage response?
Signal Sensors Transducers Effectors Response
What happens if DNA damage levels too high or persist?
Senescence or apoptosis
What is the ideal response to DNA damage?
Repair DNA and maintain function
Describe the process of base excision repair
Deamination converts incorrect base into a uracil
Uracil detected and removed, leaving base-less nucleotide
Base-less nucleotide removed, small hole in DNA backbone
Hole is filled with correct base by DNA polymerase, gap sealed by ligase
Describe the process of nucleotide excision repair
UV radiation produces (thyamine) dimer
Once dimer is defected, surrounding DNA opens to form bubble
Enzymes cut damaged region out of bubble
DNA polymerase replaces excised DNA, ligase seals backbone
Describe the process of mismatch repair
Mismatch detected in DNA
DNA strand cut, mispaired nucleotide and its neighbours removed
Missing patch replaced with correct nucleotides by DNA polymerase
DNA ligase seals gap in DNA backbone
What are the 2 ways of repairing double strand break?
Non-homologous end joining (causes lots of mutations)
Homologous directed repair
