Xeroderma pigmentosum (XP) results from defective nucleotide excision repair (NER). Which type of DNA lesion is primarily targeted by NER that is NOT repaired by base excision repair (BER)?

• A Uracil arising from cytosine deamination
• B Single-strand breaks from oxidative damage
• C Bulky adducts and pyrimidine dimers from UV-induced damage ✓
• D Methylated guanine (O6-methylguanine) from alkylating agents

Explanation

NER recognises and removes bulky helix-distorting lesions including cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts caused by UV-B radiation, as well as bulky chemical adducts. BER handles small, non-distorting base modifications (deamination, oxidation, single-strand breaks). O6-methylguanine is repaired by direct reversal via MGMT (a suicidal repair enzyme). Loss of XPC or other NER proteins in XP patients results in accumulation of UV-induced dimers, causing premature skin aging and >1000-fold increased risk of skin malignancies.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.