DNA repair relevance to cancer

Question 1

List exogenous sources of DNA damage

Answer 1

Ionising radiation, Alkylating agents, UV light, Anti-cancer agents

Question 2

What are the endogenous sources of DNA damage?

Answer 2

DNA replication errors, V(D)J recombination (genetic recombination that occurs only in developing lymphocytes), Free radicals

Question 3

What is the DNA damage response pathway?

Answer 3

Damage response: SIGNALS –> SENSORS –> TRANSDUCERS –> EFFECTORS

Question 4

Give an example of a sensor, transducer and effector

Answer 4

DNA-PK – ATM – p53

Question 5

What happens if DNA damage is too high or persists?

Answer 5

Senescence or apoptosis

Question 6

What is base-excision repair?

Answer 6

endonuclease removes single base, another enzyme removes sugar phosphate back, DNA polymerase and ligase insert correct base and join. DNA at any point in the cell

Question 7

What is nucleotide-excision repair?

Answer 7

Enzyme removes both bases and each sugar-phosphate across chains, damage induced by UV, DNA polymerase and ligase insert correct base and join

Question 8

Describe mismatch repair

Answer 8

Single base change, Occurs during/immediately after DNA replication, Endonuclease removes up to 2000bp including incorrect base, DNA polymerase fills in missing bases, ligase closes

Question 9

Describe Holliday Junction resolution

Answer 9

2 homologous duplexes are linked by D-loop, Cleavage/ligation results in holiday junction, The junction adopts a planar unfolded structure when it interacts with recombination proteins, Homoduplex –> same, Heteroduplex –> binding of different strands, Cleavage along horizontal or vertical axis, Ligation by ligase

Question 10

What is p53?

Answer 10

gene that codes for a protein that regulates the cell cycle and hence functions as a tumor suppression, very important for cells in multicellular organisms to suppress cancer, Mutated in many cancer

Question 11

When are the cell cycle checkpoints?

Answer 11

G1 is the environment favourable?
G2 is all the DNA replicated? Damage repaired?
Mitosis: Are all the chromosomes attached to the mitotic spindle

Question 12

Describe double strand break repair: non-homologous

Answer 12

protein protects ends, another protein binds to each end, then to each other to form complex, ligase can now bind to repair break.

Question 13

Describe double strand break repair: homologous

Answer 13

Break down the middle of both chains, resection of both chains, uses homologous template to repair.