Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair (NER). The most mutation-prone dimers in XP are caused by:
- A Oxidative 8-oxoguanine lesions repaired by base excision repair (BER)
- B UV-induced cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts that block RNA polymerase and cause C→T and CC→TT transitions ✓
- C Alkylation damage to guanine repaired by direct reversal (O6-methylguanine methyltransferase)
- D Double-strand breaks from ionising radiation repaired by homologous recombination
Correct answer: B. UV-induced cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts that block RNA polymerase and cause C→T and CC→TT transitions
Explanation
UV radiation induces pyrimidine-pyrimidine CPDs (TT most common) and 6-4 photoproducts. These bulky adducts are normally recognised by the global-genome NER pathway (involving XPC-RAD23B) and removed as 24–32 nt oligonucleotide fragments. Without NER (mutated XPA-XPG), CPDs persist, blocking replication and causing translesion synthesis that results in characteristic C→T transitions at dipyrimidine sites. XP patients develop multiple cutaneous malignancies in sun-exposed skin.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.