Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). The primary DNA lesion that NER corrects, formed by UV radiation, is:
- A Double-strand breaks at telomeric regions
- B Cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts between adjacent pyrimidines ✓
- C O6-methylguanine adducts from alkylating agents
- D 8-oxoguanine from reactive oxygen species
Explanation
UV-B radiation (280–315 nm) primarily causes covalent linkage between adjacent pyrimidines on the same DNA strand: cyclobutane pyrimidine dimers (CPDs, most common — thymine-thymine) and 6-4 photoproducts. These bulky adducts distort the double helix and are repaired by NER in two modes: global genome NER (GG-NER) and transcription-coupled NER (TC-NER). In XP (XPA-XPG gene defects), NER is absent — unrepaired dimers cause mutations (C→T transitions at dipyrimidine sites) and skin cancers. O6-methylguanine (option C) is repaired by MGMT (direct repair, alkyltransferase). 8-oxoguanine (option D) is repaired by base excision repair (BER).
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.