The disease xeroderma pigmentosum is caused by a defect in one of the following systems (affected individuals have an increased sensitivity to sunlight, have pigmentation abnormalities).
A. mismatch repair
B. Nucleotide Excision Repair (NER)
C. recombinational repair
D. translesion synthesis
The correct answer and explanation is:
The correct answer is B. Nucleotide Excision Repair (NER).
Xeroderma pigmentosum (XP) is a genetic disorder caused by defects in the Nucleotide Excision Repair (NER) system, which is responsible for repairing DNA damage caused by ultraviolet (UV) radiation. Individuals with XP are unable to properly repair UV-induced DNA lesions, specifically pyrimidine dimers, which are formed when UV light causes adjacent pyrimidine bases (like thymine) to bond together. This damage can lead to mutations if left uncorrected, and because the affected individuals cannot repair it efficiently, they develop a variety of symptoms including extreme sensitivity to sunlight, skin pigmentation abnormalities, and a higher susceptibility to skin cancers.
The NER system is responsible for removing bulky DNA lesions, such as those caused by UV light. This process involves the recognition of damaged regions in the DNA strand, excision of the damaged DNA, and resynthesis of the missing part using the undamaged strand as a template. XP occurs when any of the genes involved in NER are defective. For example, mutations in the XPA, XPB, XPC, XPD, XPE, XPF, and XPG genes, which are all part of the NER pathway, lead to the disease. These mutations impair the cell’s ability to properly repair UV-induced DNA damage, causing the accumulation of mutations that lead to the clinical manifestations of the disease.
To summarize, XP highlights the importance of NER in maintaining DNA integrity, especially in protecting cells from UV-induced mutations. The inability to repair DNA in the presence of UV radiation results in the development of early skin cancers and other complications in those affected.