DNA Damage II

Question 1

Mutations in Mismatch Repair

Answer 1

no EXO1
- less survival + higher chance develop lymphomas
- sterile
- HNPCC (colorectal cancer)

Question 2

Mutations in Base Excision Repair

Answer 2

no XRCC1 = death in mice, increase head/neck cancer
no FEN1 = death in mice, spontaneous mutations

Question 3

Mutations in Nucleotide Excision Repair

Answer 3

mutation to CSA + CSB (recognition)
- Cockayne syndrome = reduced growth, small head

loss of ERCC1 (excision)
- death in mice + cerebrooculofacioskeletal syndrome

Question 4

Mutations in Non Homologous End Joining

Answer 4

mutation to Ku70/80
- mice viable/fertile –> growth retardation + Scid
- premature aging
- Ku70 mutants = chance of cancer

Question 5

PARP = Poly(ADP-ribose) Polymerase

Answer 5

• effective in cancers with BRCA1/2 mutations
  PARP1
• needed for BER + contributes to HR
• prevents Ku protein binding in NHEJ
• directs DSBs away from MMEJ

Question 6

Fanconi’s Anemia

Answer 6

less blood cells = random damage and improper repair
- mutations to BRCA2 + FANC
- resolve interstrand crosslinks (ICL)
- integral fanconi complex recognize –> recruit remove
- HR to fix damaged DNA

Question 7

HR DNA Repair in Labs

Answer 7

knockout of gene = HR
- more DSB = more chance of HR

Question 8

CRISPR

Answer 8

• Cas9 directed by guide sequence to area in genome
• cause DSB –> NHEJ (inserts/deletes) or HR
• knockouts targeted gene