A child with xeroderma pigmentosum (XP) has markedly increased sensitivity to UV radiation and a 1000-fold increased risk of skin cancer. The fundamental molecular defect in the most common form (XP group A) involves failure of which DNA repair pathway?

• A Mismatch repair (MMR)
• B Base excision repair (BER)
• C Nucleotide excision repair (NER) ✓
• D Double-strand break repair (homologous recombination)

Explanation

Xeroderma pigmentosum is caused by defects in nucleotide excision repair (NER) — the pathway responsible for removing bulky UV-induced DNA adducts (particularly cyclobutane pyrimidine dimers and 6-4 photoproducts). The XPA protein (defective in XP-A) is critical for damage recognition and NER initiation. Without NER, UV damage accumulates, causing progressive freckling, photosensitivity, and a dramatically elevated risk of all skin cancers in sun-exposed areas. MMR defects cause Lynch syndrome (colorectal/endometrial cancer). BER handles oxidative DNA damage.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.