DNA And Cancer Repair

Question 1

What are the two types of DNA damage? Which is harder to repair and why?

Answer 1

Single strand damage

Double strand damage - this is much harder to repair as it doesn’t have a template to repair from

Question 2

Five exogenous sources of DNA damage

Answer 2

Ionising radiation
Alkylating agents
Mutagenic chemicals
Anti-cancer drugs
Free radicals

Question 3

Can the body withstand any amount of radiation at all?

Answer 3

Yes, the body’s repair mechanisms can withstand certain amounts of radiation, unless prolonged exposure or levels of radiation are increased.

Question 4

What are other types of DNA damage besides single and double strand breaks?

Answer 4

Deamination
Dimerisation - pyrimidine dimer
Interstrand crosslink

Replication errors can damage DNA

Also:
Apurinic site
Mismatches
Intercalating agent
Bulky addict

Question 5

What is DNA replication stress?

Answer 5

Inefficient replication that leads to replication fork slowing, stalling and/or breakage

Question 6

Describe the process of base pairs and proofreading

Answer 6

Misincorporation of base pair
Mismatch removed by DNA exonuclease - proofreading
DNA polymerase continues building molecule

In most cases, errors are detected and repaired.

Question 7

Huntington’s disease

Answer 7

Caused by replication errors
HTT gene is mutated
CAG repeats in protein
Healthy gene has 10-26 repeats
Mutated gene has 37-80 repeats

Question 8

What does the mutated protein in Huntington’s cause?

Answer 8

Neural degradation

The mutant protein aggregates in basal ganglia neurones, affecting movement.

Question 9

What are sources of DNA damage?

Answer 9

UV light
Inflammation
Metabolism
Free radicals - ROS
Air pollution
Ionising radiation
Smokinh

Question 10

Basic DNA damage response?

Answer 10

Signals
Sensors
Transducers
Effectors
- cell cycle transitions
- apoptosis
- transcription
- DNA repair (mostly)

Question 11

What is the purpose of cell cycle checkpoints?

Answer 11

G1 checkpoint checks that organelles have been duplicated correctly.

G2 checkpoint checks that all the DNA has been replicated and that any DNA damage is repaired.
- this checkpoint allows temporary arrest of cell cycle to repair DNA before mitosis

Checkpoint in mitosis checks that all the chromosomes have been properly attached to the mitotic spindle.

Question 12

What are the 3 types of single strand break repair?

Answer 12

Base excision repair
Nucleotide excision repair
Mismatch repair

Question 13

Describe the process of base excision repair.

Answer 13

Faulty base is detected and removed, leaving a base-less nucleotide.
Base-less nucleotide is removed, leaving small hole in DNA backbone.
Hole is filled with the correct nucleotide by DNA polymerase, gap is sealed by ligase.

Question 14

Describe the process of nucleotide excision repair.

Answer 14

UV radiation produces thymine dimer.
Dimer detected; surrounding DNA opens to form bubble.
Enzymes cut damaged region out of the bubble.
DNA polymerase replaces the excised DNA and ligase seals the backbone.

Question 15

Describe the process of mismatch repair.

Answer 15

Mismatch is detected.
New DNA strand is cut, mispaired nucleotide + neighbours is removed.
Missing patch is replaced with correct nucelotides by DNA polymerase.
DNA ligase seals gap in DNA backbone.

Question 16

What are the two types of double strand break repair?

Answer 16

Non-homologous end joining

Homology-directed repair

Question 17

Describe the process of non-homologous end joining.

Answer 17

Broken ends are bound by Ku70/80 proteins.
DNA-PKcs complex is recruited, followed by Artemis and MRN - resection (trimming of the excess base pairs) occurs
DNA ligase repairs break
- new DNA may not be an exact copy of the original
=> downstream consequences

Question 18

Describe the process of homology-directed repair.