Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). XP patients develop skin cancers on sun-exposed areas. In global genome NER (GG-NER), the initial damage recognition step involves which molecular complex?
- A XPC-RAD23B complex recognising helix distortion caused by bulky DNA adducts or pyrimidine dimers ✓
- B MSH2/MSH6 (MutSalpha) heterodimer scanning for base pair mismatches
- C ATR-ATRIP complex recognising RPA-coated single-stranded DNA at stalled replication forks
- D Ku70/Ku80 heterodimer binding directly to UV-induced cyclobutane pyrimidine dimers
Explanation
Global genome NER (GG-NER) can detect bulky lesions throughout the genome regardless of transcriptional activity. The initial recognition step involves the XPC-RAD23B complex (with UV-DDB/DDB2 assisting for CPD recognition), which identifies helix distortion caused by bulky adducts (e.g., cyclobutane pyrimidine dimers, 6-4 photoproducts from UV; benzo[a]pyrene adducts). XPC-RAD23B binding recruits TFIIH, which contains XPD and XPB helicases that open the helix around the lesion. XPA verifies the damage and RPA stabilises single-stranded DNA, after which XPG and XPF-ERCC1 nucleases excise a 25-30 nucleotide oligonucleotide containing the lesion. MSH2/MSH6 is mismatch repair; ATR-ATRIP is the replication stress response; Ku70/Ku80 is non-homologous end joining for DSBs.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.