Week 5 L1: DNA REPAIR

Question 1

Why does damaged DNA need to be repaired?

Answer 1

leads to 80 - 90% of human cancers

Question 2

What are some examples of how DNA can be damaged?

Answer 2

Many enviromental factors 
replication errors
UV light 
Crosslinking agents 
alkylation 
Ionising Radiation 
Missing base 
Altered base 
incorrect base 
Oxygen radical toxicity

Question 3

What is the most common type of damage?

Answer 3

single-stranded breaks

50,000 events a day

Question 4

How many people will die of cancer?

Answer 4

1 in 3

Question 5

What are some agents used in chemotherapy?

Answer 5

topoisomerase inhibitors; e.g. topo 1

DSB inducing agents

DNA cross linking agents

Question 6

What are some examples of DNA cross linking agents?

Answer 6

Cisplatin, nitrogen mustard

Question 7

What is the effects of alkylation agents?

Answer 7

Attack the hetero atoms on on DNA bases and can result in nitrogen mustard for example

Question 8

What does nitrogen mustard attack?

Answer 8

N7 of guanine

Question 9

What is an example of a DNA crosslinking agents?

Answer 9

cisplatin

Question 10

What are the structures of cisplatin?

Answer 10

square planar complexes
Pt + 2 Nh3 + 2Cl
Cl relatively easily displaced so can crosslink the N7 of 2 guanines for example.

Question 11

What is the effect of UV light?

Answer 11

CROSSLINKING ADJACENT THYMINE NUCLEOBASES (TPT seq)

Question 12

What are the 2 types of crosslinking that can occur with thymine dimers?

Answer 12

cyclobutane dimer
form a cyclobutane ring

6-4 photoproduct

Question 13

What is the effect of Oxidative DNA damage?

Answer 13

damage backbone leading to disintegration of the deoxyribose ring
–> double stand breaks
Damage to thymine.

Question 14

What is crosslinkage?

Answer 14

occur within the same strand (intrastrand) or between opposite strands of double-stranded DNA (interstrand). These adducts interfere with cellular metabolism, such as DNA replication and transcription, triggering cell death.