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