[W9] DNA Repair Flashcards
(32 cards)
What is DNA damage?
A physical or chemical abnormality in the structure of DNA that may impair replication or transcription.
How is DNA damage different from mutation?
Damage affects DNA structure; a mutation is a change in base sequence.
Why is DNA repair important?
Prevents mutations, aging, and diseases like cancer by maintaining genome integrity.
What are the spontaneous sources of DNA damage?
- Replication errors
- Tautomeric shifts
- Depurination
- Deamination
Name common chemically induced DNA damages.
- Alkylation (e.g., EMS, mustard gas)
- Deamination (e.g., nitrous acid)
- Oxidation (e.g., ROS)
- Intercalating agents (e.g., ethidium bromide)
How does radiation cause DNA damage?
- Ionizing radiation → DSBs, ROS
- UV radiation → pyrimidine dimers (CPDs, 6-4PPs)
What is a transition mutation?
A purine replaces a purine or a pyrimidine replaces a pyrimidine.
What is a transversion mutation?
A purine is replaced by a pyrimidine, or vice versa.
What are the main types of DNA repair?
- Direct repair
- Base excision repair (BER)
- Nucleotide excision repair (NER)
- Mismatch repair (MMR)
- Double-strand break repair (HR and NHEJ)
What is direct repair?
Restores damaged nucleotides to their original structure without replacing them.
What is photoreactivation?
Light-dependent repair of pyrimidine dimers by photolyase.
What does MGMT do?
Repairs alkylated guanine (O6-methylguanine) via a suicide reaction.
What initiates Base Excision Repair (BER)?
DNA glycosylases remove the damaged base.
What determines BER pathway length?
- Short patch: Pol β
- Long patch: Pol δ/ε
What enzyme cuts the AP site?
AP endonuclease (e.g., APE1).
What kind of damage does Nucleotide Excision Repair (NER) correct?
Bulky helix-distorting lesions like UV-induced pyrimidine dimers.
What are the two NER sub-pathways?
- Global genome repair (GG-NER)
- Transcription-coupled repair (TC-NER)
What protein detects damage in GG-NER?
XPC.
What detects damage in TC-NER?
Stalled RNA polymerase recruits CSA/CSB.
What is the role of TFIIH in NER?
Helicase activity to unwind DNA for excision and repair.
What does Mismatch Repair (MMR) fix?
Base mismatches and small insertion/deletion loops after replication.
How does MMR distinguish strands?
Recognizes methylation status (in prokaryotes) or Okazaki fragments/daughter strand markers (in eukaryotes).
What are the two major double-strand break (DSB) repair mechanisms?
- Nonhomologous end joining (NHEJ)
- Homologous recombination (HR)
What is NHEJ?
Joins blunt ends without needing a homologous template; error-prone.
