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