A 9-year-old boy develops freckling and blistering sunburns on sun-exposed skin followed by poikiloderma, and later multiple squamous cell carcinomas before age 10. Cultured skin fibroblasts show defective repair of ultraviolet-induced DNA damage. The specific repair pathway implicated is:

• A Mismatch repair of replication errors
• B Nucleotide excision repair of bulky UV photoproducts ✓
• C Base excision repair of oxidative lesions
• D Nonhomologous end joining of double-strand breaks

Explanation

Xeroderma pigmentosum results from defects in nucleotide excision repair, the pathway that removes bulky helix-distorting lesions such as cyclobutane pyrimidine dimers and 6-4 photoproducts induced by ultraviolet light. Defective NER leaves these adducts unrepaired, causing extreme photosensitivity, pigmentary change, and early skin cancers. Mismatch repair deficiency underlies Lynch syndrome, base excision repair handles small chemical modifications, and nonhomologous end joining defects relate to radiosensitivity syndromes such as ataxia-telangiectasia.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.