A patient with xeroderma pigmentosum (XP) has an extreme predisposition to UV-induced skin cancer. The biochemical defect involves failure of which DNA repair pathway?

• A Base excision repair (BER) — removing oxidised bases
• B Nucleotide excision repair (NER) — removing bulky helix-distorting lesions such as pyrimidine dimers ✓
• C Mismatch repair (MMR) — correcting incorporation errors during replication
• D Homologous recombination repair — fixing double-strand breaks

Explanation

UV radiation causes cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts — bulky, helix-distorting lesions recognised and removed by nucleotide excision repair (NER). XP is caused by mutations in any of the XPA-XPG genes encoding NER proteins; unrepaired CPDs lead to C→T transition mutations in proto-oncogenes and tumour suppressor genes (notably p53), causing multiple squamous and basal cell carcinomas. BER handles small oxidised/alkylated bases; MMR handles replication errors; HR handles DSBs (BRCA1/2).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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