Nucleotide excision repair (NER) is defective in xeroderma pigmentosum (XP). NER removes bulky adducts (from UV) by a cut-and-patch mechanism. The FIRST recognition step in global genome NER (GGR) is performed by:
- A TFIIH complex, which unwinds DNA at the lesion site using its XPB and XPD helicase subunits
- B RPA (replication protein A), which binds single-stranded DNA exposed after XPC loading
- C XPC-RAD23B complex, which recognizes helical distortion in the DNA double strand ✓
- D XPA protein, which verifies the chemical lesion by direct contact with the damaged base
Explanation
In global genome NER (GGR), the XPC-RAD23B (hHR23B) complex is the primary damage sensor that scans chromatin and recognizes helical distortion caused by bulky adducts (cyclobutane pyrimidine dimers, 6-4 photoproducts, cisplatin crosslinks), even without directly contacting the damaged base. XPC recruits TFIIH (which unwinds DNA via XPB/XPD helicases), then XPA verifies the lesion and coordinates assembly of dual incision nucleases XPG (3' cut) and XPF-ERCC1 (5' cut), releasing a ~30 nt oligonucleotide containing the lesion. In transcription-coupled NER (TC-NER), the RNA polymerase stalled at the lesion serves as the initial sensor.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.