DNA repair and Cancer Flashcards
(10 cards)
How many checkpoints are there in cell cycle and what are they?
3
G1 checkpoint Before s phase - is the environment favourable?
G2 checkpoint before mitosis- is all Dna replicated?and is all damaged repaired?
Checkpoint in mitosis when chromosomes pulled apart (anaphase) - are all chromosomes attached to the mitotic spindle properly?
What are the three main response pathways to dna damage?
Senescence - permanent cell cycle arrest
Profileration - DNA repair
Apoptosis - cell death
Which response pathways are used if DNA damage levels are too high or persist
Senescence or apoptosis
What is the most ideal response pathway?
Proliferation
What are the diff types of dna repair
Base-excision repair - remove base leaving hole in DNA backbone and then replaced by a DNA polymerase and gap sealed by DNA ligase.
Nucleotide-excision repair - remove patch of nucleotides with enzymes and replace using DNA polymerase and sealed with ligase
Mismatch repair - e.g G paired with T. New strand is cut and mismatched nucleotide and adjacent ones removed and then replaced by polymerase and ligase.
Recombinational repair - if theres a double stand damage. Two types to include: non-homologous end joining where recognised by proteins and then you cut off damaged ends then ligate broken ends (not good as can cause mutations) and homologous-directed repair
Explain what happens during homologous end pairing
Look at slides lol
Explain the multi-step cancer model
DNA replication stress increases mutations
Mutations increases which increases likelihood of it becoming malignant
Therefore increasing carcinogenesis
Normal -> premalignant -> malignant
How does cancer evolve?
Cancer evolves to have Intra-tumour heterogeneity
This means all of tumour cells aren’t identical and are sub clones of each other so are varied
Heterogeneity promotes tumour evolution
Heterogenous tumours are formed due to mutation accumulation and dna repair factor mutations
How can chemotherapy lead to cancer evolution?
If the tumour is heterogenous:
differential sensitivity - a subclone is resistant to the therapy and continues to grow so cancer comes back whilst other subclones die.
Chemotherapy-induced mutagenesis - therapy shrinks tumour yet mutates one of the subclones which is resistant to therapy and resistant cancer grows back
What are synthetic lethality strategies?
Treatment for cancer by targeting dna repair genes causing cell death of cancer cells
An example is the PARP inhibitor
It causes single strand breaks to become double strand breaks killing cancer cells which don’t have active repair mechanism(gene) for double strand breaks.
Normal cells not affected as these have repair genes
