Xeroderma pigmentosum (XP) patients have extreme UV sensitivity and very high rates of skin cancers. XP complementation group A (XPA) involves a protein that recognizes bulky DNA adducts. Which DNA repair pathway is defective in XP?
- A Base excision repair (BER) — removes small modified bases like 8-oxoguanine
- B Nucleotide excision repair (NER) — removes bulky helix-distorting lesions like cyclobutane pyrimidine dimers ✓
- C Mismatch repair (MMR) — corrects replication errors like G:T mismatches
- D Non-homologous end joining (NHEJ) — repairs double-strand breaks
Correct answer: B. Nucleotide excision repair (NER) — removes bulky helix-distorting lesions like cyclobutane pyrimidine dimers
Explanation
NER recognizes and removes bulky, helix-distorting adducts including UV-induced cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. NER involves ~30 proteins: damage recognition → dual incision (at ~25 nucleotides) → oligonucleotide removal → gap-filling (by DNA polymerase delta/epsilon) → ligation. XP genes (XPA-G, XPV) encode NER components. XPA helps verify damage and recruits repair machinery. BER handles small lesions without helix distortion. MMR corrects polymerase errors. NHEJ repairs DSBs — defective in radiation sensitivity syndromes.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.