AT L2 DNA strand breakers - bleomycins

Question 1

What are bleomycin

Answer 1

Glycopeptide antibiotics isolated from Strep verticillus used in combo chemo

Question 2

s/e of belomycins

Answer 2

lung inflammation and fibrosis

Question 3

How do bloemycins work?

Answer 3

bind transition metals (Fe & Cu) and oxygen to catalyse ss and ds DNA legions

Question 4

What is the damage of bleomycins similar to

Answer 4

ionising radioation

Question 5

How are bleomycins taken up into cells?

Answer 5

too polar for diffusion but thought that the positively charged tail is involved in uptake

Question 6

What is the action of bleomycins on a cell

Answer 6

cell line and genotype dependent but generally cell cycle arrest, apoptosis and mitotic cell death

Question 7

structure of a bleomycin

Answer 7

dishaccaride, metal binding region, linker, bithiazole +ve charged tail

Question 8

Mode of action of bleomycins

Answer 8

1. double ring tail slots into DNA like an intercalator
2. charged tail winds up in grove oposite
3. ss cleavage at pyrimidine
   4 reactivation and reorganisation of bleomycin for ds cleavage (linker and flexibitlity of tail thought to be responsible)

Question 9

What sort of damage is caused by bleomycin?

Answer 9

stepped and blunt end.

Both ds so must use double strand repair.

Question 10

2 pathways of double strand break repair that are error prone

Answer 10

non-homologous end joining (NHEJ) and break-induced replication (BIR)

Question 11

steps of double strand break repair

Answer 11

1. Peel back a strand leaving one longer than the other
2. You need DNA sequence that ideally an exact match. Unzip it and feed loos ends to it to pair up.
3. Wind up and build in the bits missing usinng open strand as a template