DNA Repair

Question 1

Define DNA mutation

Answer 1

Any change from the normal DNA sequence

Question 2

What are the types of point mutation?

Answer 2

• Deletion
• Insertion
• Substitution

Question 3

What are the two types of substitution mutations? What is the difference between them?

Answer 3

**Transition **substitutions involve purine to purine, or pyrimidine to pyrimidine substitutions. Whereas transversion substitutions are purine to pyrimidine substitutions or vice versa.

Question 4

What are some exogenous examples of DNA damagin sources?

Answer 4

• Ionising radiation
• UV radiation
• Chemicals

Question 5

What is thymine cross-linking?

Answer 5

A mutation that causes two adjacent thymine bases to become covalently attached to form a thymine dimer. Induced by UV radiation.

Question 6

What are examples of endogenous DNA damage?

Answer 6

• Hydrolysis
  
  • depurination
  • deamination
• Oxidation

Question 7

What is depurination?

Answer 7

Endogenous DNA damage that causes the loss of an adenine or guanine base.

Question 8

What is deamination?

Answer 8

Endogenous DNA damage which causes the loss of an amino group.

This can change cytosine to uracil, adenine to hypoxanthine, or 5 methylcytosine to thymine.

Question 9

What is oxidative damage?

Answer 9

Damage cause by **ROS **(reactive oxygen species) that are produced as a byproduct of metabolism.

ROS attack purine and pyrimidine rings. This can change guanine to 8-hydroxyguanine which pairs with A instead of C. It can also cause **helical distortion **by creating additional covalent bonding between bases and the sugar-phosphate backbone.

Question 10

What is DNA mismatch repair (MMR)?

Answer 10

A system for recognizing and **repairing **incorrect insertions, deletions, and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairing some forms of DNA damage

Question 11

What does direct repair do?

Answer 11

It reverses the DNA damage directly. It is infrueqently used, and can remove methyl groups.

Question 12

What does base excision repair (BER) do?

Answer 12

It removes **single **damaged bases, carries out single strand break repair, and is the main protector against metabolism damage.

Question 13

What is the process of base excision repair (BER)?

Answer 13

• DNA glycolases identify and remove the damaged base
• AP endonuclease and T phosphodiesterase cut the sugar-phosphat backbone
• DNA polymerase fills the gap and DNA ligase seals the nick

Question 14

What does nucleotide excision repair (NER) do?

Answer 14

Removes thymine dimers and large chemical adducts

Question 15

What is the process of nucleotide excision repair (NER)?

Answer 15

• The damaged bases are detected
• Helicases and nucleases act to open up and cut either side of the bases
• DNA polymerase fills the gap and DNA ligase seals the nick

Question 16

What is homologous recombination repair (HR)?

Answer 16

Repairs double-stranded breaks. Requires sister chromatid.

Question 17

What does non-homologous end joining (NHEJ) do?

Answer 17

It repairs **double-stranded **breaks. Two broken ends are joined regardless of the sequence.

Question 18

List the types of repair mechanisms (6).

Answer 18

• Direct
• BER (Base excision)
• NER (Nucleotide excision)
• MMR (Mismatch)
• HR (Homologous recombination)
• NHEJ (Non-homologous end joining)

Question 19

What are some examples of defective repair mechanisms?

Answer 19

• BER: colon cancer
• NER: xerodermia pigmentosa
• MMR: HNPCC (hereditary nonpolyposis colon cancer)
• HR: bloom syndrome
• NHEJ: leukaemia