DNA Damage & Repair

Question 1

Explain how the structure of DNA bases makes them particularly targeted by electrophiles.

Answer 1

Bases are flat rings, allowing delocalisation of electrons, therefore being an easy target for a chemical that requires electrons

Question 2

Removal of which group converts thymine to uracil?

Answer 2

CH3 methyl

Question 3

Deamination of cytosine gives

Answer 3

Uracil, effectively thymine

Question 4

Deamination of adenine gives

Answer 4

Hypoxanthine

Question 5

Deamination of guanine gives

Answer 5

Xanthine

Question 6

Adding an amine to thymine gives

Answer 6

5-methyl cytosine

Question 7

Oxidation of thymine gives

Answer 7

Thymine glycol

Question 8

Xrays produce which chemical that damages DNA?

Answer 8

Oxygen free radicals from cellular damage

Question 9

What does photodamage result in?

Answer 9

Pyrimidine dimers

Question 10

What do you call the carcinogens from smoke?

Answer 10

Polycyclic aromatic hydrocarbons

Question 11

Name three dangerous products of radiation, such as from flights

Answer 11

Superoxide radicals
Hydroxyl radicals
Oxygen free radicals

Question 12

Two of these products of radiation cause the same damage to DNA. Which are these and what do they do to DNA?

Answer 12

Superoxide radicals and hydroxyl radicals form nicks (loss phosphodiester bond)

Question 13

Oxygen free radicals causes 4 types of damage. Name these.

Answer 13

Strand breaks
Open-ringed purines
8-hydroxypurines
Pyrimidine glycols

Question 14

Which transcription factor is turned on in response to DNA damage?

Answer 14

p53

Question 15

Name 5 types of DNA repair and link these to DNA damage

Answer 15

Nucleotide excision repair - for nicks
Base excision repair - for bulky adducts on bases
Direct DNA repair - e.g. methylated bases or pyrimdine dimers
DNA mismatch repair
Double strand repair

Question 16

Name four natural biproducts of oxidative metabolism

Answer 16

Singlet oxygen
Peroxide radicals
Hydrogen peroxide
Hydroxyl radicals

Question 17

Give two examples of direct DNA repair

Answer 17

Photolyase - removes the thymine dimers

MGMT (O6 Methylguanine methyltransferase) - removes methyl/alkyl group on guanine

Question 18

Which gene produces proteins responsible for recognising the incorrect bases in DNA mismatch repair?

Answer 18

MSH2 genes

Question 19

Which gene produces proteins responsible for cutting out the incorrect bases in DNA mismatch repair?

Answer 19

MLH1 genes

Question 20

Name four enzymes involved in base excision repair and their functions

Answer 20

DNA glycolase - removes base
AP endonuclease - removes sugar phosphate backbone
DNA polymerase - adds new base
DNA ligase - glues together the backbone

Question 21

Name four enzymes involved in nucleotide excision repair and their functions

Answer 21

Endonuclease - removes base and backbone
Helicase - unwinds the DNA
DNA polymerase - adds new base
DNA ligase - glues together the backbone

Question 22

Name a type of DNA repair which, when mutated or absent, can be associated with diseases. Name three of these diseases

Answer 22

Nucleotide excision repair:
Xeroderma Pigmentosa
Trichothiodystrophy
Cockayne’s syndrome

Question 23

Signs and symptoms of Xeroderma Pigmentosa

Answer 23

Increases sensitivity to light
Pigmented lesions on skin
Increased risk of skin cancer

Question 24

Signs and symptoms of Trichothiodystrophy

Answer 24

Brittle hair
Ichthyosis (fish like scales on skin)
Short stature
Facial abnormalities

Question 25

Signs and symptoms of Cockayne’s syndrome

Answer 25

Limb and neurological abnormalities

Question 26

Which type of DNA repair is also seen in meiosis?

Answer 26

Double strand repair - similar to homologous recombination

Question 27

Briefly explain DNA double strand repair

Answer 27

Nucleotides are added until the strands meet

Question 28

Name three ways in which therapeutic cancer agents can incidentally cause DNA damage.

Answer 28

Alkylating agents - e.g. oxaliplatin, chlorambucil
Bulky adduct formation - e.g. cisplatin
Induction of double strand breaks - radiation

Question 29

Briefly outline how new chemicals can be tested for carcinogenic properties.

Answer 29

Ames test using bacteria
Invitro micronucleus assay
Murine bone marrow micronucleus assay

Question 30

Which protein is involved in DNA double strand repair and what does it do?

Answer 30

Ku proteins hold the strands on either side whilst new nucleotides are added.