TR

DNA Repair

DNA Repair Mechanisms

  • Direct chemical reversal of the damage
  • Excision repair: damaged base or bases are removed and then replaced with the correct ones
    • Base Excision Repair
    • Nucleotides Excision Repair
    • Mismatch Repair

Base Excision Repair

  • DNA glycosylase removes the damaged base
    • Occurs about 20,000 times a day in every cell
  • Removal of its deoxyribose phosphate
    • Produces a gap
  • Correct nucleotide is incorporated by DNA polymerase β
  • Ligation

Nucleotide Excision Repair

  • The damage is recognized by one or more protein factors that assemble at the location.
    • The DNA is unwound producing a "bubble".
  • Cuts are made on both the 3’ side and the 5’ side of the damaged area and the tract containing the damage can be removed
  • Using the opposite strand as a template DNA Pol α or ε fills in the correct nucleotides
    • This is followed by Ligation
  • Nucleotide-excision repair proceeds most rapidly on the DNA strand that is serving as the template for transcription

Mismatch Repair

  • Mismatch repair deals with correcting mismatches of the normal bases
  • Accounts for 99% of all repairs
  • Follows behind replication fork
  • Recognition of mismatch require protein complex
  • Excision of mismatch
  • DNA synthesis by Pol 𝛼 or 𝜀

Repairing Strand Breaks

  • Single-Strand Breaks: uses the same enzyme systems that are used in base excision repair
  • Double-Strand Breaks
    • Nonhomologous End Joining = Direct joining of the broken ends
    • Nonhomologous Recombination