Xeroderma pigmentosum is caused by defective nucleotide excision repair (NER). Which type of DNA lesion does NER specifically recognize and repair, and which is the rate-limiting step?
- A Single-strand breaks; rate-limiting step is nick ligation by DNA ligase
- B Mismatched bases; rate-limiting step is mismatch recognition by MutS homologues
- C Bulky helix-distorting lesions (e.g., UV-induced pyrimidine dimers, benzo[a]pyrene-DNA adducts); rate-limiting step is damage recognition ✓
- D Oxidised bases; rate-limiting step is glycosylase-mediated base excision
Explanation
NER repairs bulky, helix-distorting DNA lesions including UV-induced cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts, as well as large chemical adducts (e.g., cisplatin cross-links, benzo[a]pyrene adducts). The rate-limiting step is damage recognition: in global-genome NER, XPC-Rad23B recognizes the distortion; in transcription-coupled NER, stalled RNA polymerase II signals repair. XPD and XPB (subunits of TFIIH) unwind DNA; XPG and XPF-ERCC1 excise a 24–32 nt oligonucleotide containing the lesion; DNA polymerase delta/epsilon resynthesises the patch. Defects in XP genes A-G cause xeroderma pigmentosum with extreme UV sensitivity and >1000-fold increased skin cancer risk.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.