Defect in xeroderma pigmentosum (Repeat)
**Core Concept**
Xeroderma pigmentosum is a rare genetic disorder characterized by extreme sensitivity to ultraviolet (UV) light, leading to an increased risk of skin cancers. This condition is caused by mutations in genes involved in the repair of DNA damage induced by UV radiation.
**Why the Correct Answer is Right**
The correct answer is nucleotide excision repair (NER). NER is a DNA repair mechanism that corrects bulky DNA damage, such as those caused by UV radiation, by removing a stretch of 24-32 nucleotides surrounding the lesion. In xeroderma pigmentosum, mutations in the genes encoding the NER proteins (e.g., XPA, XPB, XPC, XPD, XPE, XPF, and XPG) impair the ability to repair UV-induced DNA damage, leading to an accumulation of mutations and increased cancer risk. The NER pathway is essential for maintaining genome stability in response to UV radiation.
**Why Each Wrong Option is Incorrect**
**Option A:** Mismatch repair is a different DNA repair pathway that corrects errors in DNA replication and recombination, such as mismatched bases or insertions/deletions. It is not directly involved in repairing UV-induced DNA damage.
**Option B:** Base excision repair (BER) is another DNA repair pathway that corrects damage to individual bases, such as oxidized or alkylated bases. While BER is important for maintaining genome stability, it is not primarily responsible for repairing UV-induced DNA damage.
**Option D:** Double-strand break repair is a DNA repair mechanism that corrects breaks in both strands of DNA, often resulting from ionizing radiation or DNA replication errors. It is not directly involved in repairing UV-induced DNA damage.
**Clinical Pearl / High-Yield Fact**
Xeroderma pigmentosum is a rare genetic disorder, but its clinical features are a classic reminder of the importance of DNA repair mechanisms in maintaining genome stability. The condition's sensitivity to UV light and increased cancer risk highlight the critical role of NER in protecting against UV-induced DNA damage.
**✓ Correct Answer: C. Nucleotide excision repair**