Overview
This part of Lecture 7 covers major DNA repair mechanisms, detailing how cells fix different types of DNA damage to maintain genetic integrity.
Mismatch Repair (MMR)
- Mismatch repair fixes base-pairing errors missed by DNA polymerase proofreading.
- The system distinguishes the new DNA strand by its lower methylation compared to the parental strand.
- Key enzymes: MutS detects mismatches, MutL is recruited, and MutH (an endonuclease) nicks the new strand near the error.
- Exonuclease removes a segment containing the mismatch, DNA polymerase resynthesizes DNA, and DNA ligase seals the strand.
- Endonuclease cuts the DNA backbone, while exonuclease removes bases from the break.
Base Excision Repair (BER)
- Base excision repair removes modified or damaged bases (e.g., 8-oxoguanine, 3-methyladenine, uracil in DNA).
- Glycosylase enzyme removes the damaged base, leaving an abasic (AP) site.
- AP endonuclease cleaves the backbone at the AP site; DNA polymerase adds the correct nucleotide and DNA ligase seals the nick.
- Uracil DNA glycosylase specifically removes uracil from DNA caused by deamination of cytosine.
Nucleotide Excision Repair (NER)
- NER repairs bulky lesions (e.g., thymine dimers) not fixed by BER.
- A nuclease excises a section of the damaged strand, DNA polymerase fills the gap, and DNA ligase seals it.
- Human NER requires about 30 genes; mutations cause disorders like Xeroderma pigmentosum (XP) and Cockayne syndrome.
Photoreactivation (Light Repair)
- Photoreactivation repairs thymine dimers using the enzyme photolyase, activated by light (found only in prokaryotes).
- Photolyase breaks covalent bonds in thymine dimers, returning DNA to its normal state.
- Humans lack this enzyme and rely on NER for UV-induced damage.
Post-Replication Repair & Double-Stranded Breaks
- Post-replication repair fixes gaps left opposite unrepaired lesions (like thymine dimers) by using recombination and the undamaged template.
- RecA-mediated recombination allows exchange or copying from a sister chromatid or homologous chromosome.
- Double-stranded breaks (caused by ionizing radiation) are repaired by strand invasion and synthesis using a sister chromatid as a template.
Key Terms & Definitions
- Mismatch Repair (MMR) — System correcting replication errors missed by proofreading.
- Endonuclease — Enzyme that cuts within a DNA strand.
- Exonuclease — Enzyme that removes nucleotides from the ends or breaks in DNA.
- Base Excision Repair (BER) — Repairs small, non-bulky base modifications.
- Glycosylase — Enzyme that removes damaged bases from DNA.
- AP Site — DNA site missing a base (apurinic/apyrimidinic).
- Nucleotide Excision Repair (NER) — Repairs bulky DNA lesions by removing and resynthesizing a segment.
- Photoreactivation — Light-dependent repair of thymine dimers (prokaryotes only).
- Recombination — Exchange or copying of DNA sequences for repair.
- Double-Stranded Break (DSB) — Break through both DNA strands, often repaired by recombination.
Action Items / Next Steps
- Read textbook Chapter 16, focusing on DNA repair mechanisms.
- Answer textbook questions 2–16 from Chapter 16.
- Collaborate with classmates or post questions on the discussion board if you need help.