Genetics

Question 1

1a. Describe the mechanism of base excision repair (BER) (4 points)

Answer 1

• used to repair single strand breaks and single base damage
• base is removed by DNA glycosylase
• sugar phosphate is removed by AP endonuclease (5’ incision) and dRP lyase (flap removal)
• the gap is filled by DNA polymerase and ligase

Question 2

1b. Describe the mechanism of non-homologous end joining (NHEJ) (4 points)

Answer 2

• used to repair double strand DNA breaks and intra-stand crosslinks
• when breaks are ‘clean’, the broken ends are held together by Ku70/80, and joined by DNA ligase
• when breaks are ‘dirty’, broken ends are processed by nucleases, kinases, Artemis etc.
• ends are filled by DNA polymerase and ligated by XLF/XRCC4 ligase complex IV

Question 3

1c. Describe the mechanism of homologous recombination (HR) (4 points)

Answer 3

• used to repair double strand breaks and intra-strand crosslinks
• broken DNA molecule processed to give long 3’ ssDNA sections
• rad51 (recombinase) forms filaments along ssDNA with the help of mediator proteins (rad52, 54, 55, 57) which invade homologous molecules
• branched-out undamaged strand acts as a template to repair the break
  DNA synthesis and ligation then occurs

Question 4

1d. Describe the mechanism of nucleotide excision repair (NER) (4 points)

Answer 4

• used to repair intra-strand crosslinks and bulky adducts
• DNA damage is recognised and helicases [TFIIH (XPB, XPD)] unwind DNA around damage
• nucleases [XPF] cut the section of damaged strand 5’ to 3’
• DNA polymerase and DNA ligase fills in the gap