DNA repair

Single strand

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Nucleotide excision repair

• Mechanism:
  • Specific endonucleases remove the oligonucleotides containing damaged bases.
  • DNA polymerase and ligase fill and reseal the gap, respectively.
  • Repairs bulky helix-distorting lesions (e.g., pyrimidine dimers).
• When:
  • Occurs in G₁ phase of cell cycle.
• Clinical relevance:
  • Defective in xeroderma pigmentosum (inability to repair DNA pyrimidine dimers caused by UV exposure).
  • Presents with dry skin, photosensitivity, skin cancer.

Exonuclease vs. Endonuclease

Feature	Exonuclease	Endonuclease
Action	Removes nucleotides from the ends (5’ or 3’) of a nucleic acid chain.	Cleaves phosphodiester bonds within a nucleic acid chain.
Products	Single mononucleotides, released one at a time.	Oligonucleotide fragments of varying sizes.
Specificity	Generally not sequence-specific.	Can be non-specific (e.g., DNase I) or highly sequence-specific (e.g., restriction enzymes).
Key Example	DNA Polymerase Proofreading: 3’→5’ exonuclease activity removes mismatched bases during replication.	Restriction Enzymes: Recognize and cut specific palindromic DNA sequences (e.g., for RFLP, cloning).
Circular DNA	Cannot act on circular DNA (no free ends).	Can act on circular DNA.

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Base excision repair

• Mechanism:
  • Base-specific Glycosylase removes altered base and creates AP (apurinic/apyrimidinic) site.
  • AP-Endonuclease cleaves 5′ end, removing one or more nucleotides.
  • AP-Lyase cleaves 3′ end.
  • DNA Polymerase-β fills the gap.
  • DNA ligase seals it.
• Mnemonic:
  • “GEL Please.”
• When:
  • Occurs throughout cell cycle.
• Clinical relevance:
  • Important in repair of spontaneous/toxic deamination.

Mismatch repair

• Mechanism:
  • Mismatched nucleotides in newly synthesized strand are removed and gap is filled and resealed.
• When:
  • Occurs predominantly in S phase of cell cycle.
• Clinical relevance:
  • Defective in Lynch syndrome.