Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair (NER). Which specific step of NER is defective in the most common form (XP-C)?
- A XPC-RAD23B complex — initial damage recognition in global genome NER ✓
- B ERCC2/XPD helicase — unwinding DNA around the lesion
- C PCNA — loading at the repair site
- D XPG endonuclease — 3' incision
Correct answer: A. XPC-RAD23B complex — initial damage recognition in global genome NER
Explanation
In global genome NER (GG-NER), XPC complexed with RAD23B and CETN2 is the initial DNA damage sensor — it recognizes helix distortions caused by UV-induced cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. XP-C mutations are the most common form of XP. After XPC binding, TFIIH (containing XPD and XPB helicases) unwinds DNA ~30 bp; XPA verifies damage; XPG (3' incision) and XPF-ERCC1 (5' incision) excise a ~25–30 nucleotide oligomer; DNA polymerase delta fills in the gap. XPD mutations cause XP-D and trichothiodystrophy depending on mutation location.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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