A 1-year-old girl presents with skin blisters and freckling. What DNA repair mechanism is most likely defective in her condition?

• A. Base excision repair
• B. Mismatch repair
• C. Nucleotide excision repair
• D. Recombination repair

Answer: (C)

The presentation of skin blisters and freckling in the 1-year-old girl is suggestive of a condition related to impaired DNA repair, specifically related to handling damage caused by ultraviolet (UV) radiation. The symptoms described are characteristic of xeroderma pigmentosum (XP), a genetic condition where individuals have a heightened sensitivity to sunlight and are prone to skin malignancies.

Nucleotide excision repair is the DNA repair mechanism primarily responsible for correcting bulky DNA adducts caused by UV light, which can result in the formation of pyrimidine dimers. In individuals with a defect in nucleotide excision repair, the cellular ability to identify and remove these DNA lesions is compromised, leading to the accumulation of unrepaired damage, which manifests clinically as skin blisters and the pigmentation abnormalities noted.

The other DNA repair mechanisms listed—base excision repair, mismatch repair, and recombination repair—are responsible for different types of DNA damage but are not primarily involved in repairing UV-induced lesions. Therefore, the connection between the symptoms observed and the specific type of DNA repair defect leads to the conclusion that nucleotide excision repair is the most likely mechanism that is defective in this child's condition.