Question

The human disease known as xeroderma pigmentosum (XP) arises from mutations in at least seven different genes. The resulting deficiencies are generally in enzymes involved in some part of the pathway for nucleotide excision repair. The various types of XP are denoted A through G (XPA, XPB, etc.), with a few additional variants lumped together under the label XP-V. Cultures of fibroblasts from healthy individuals and from patients with XPG are irradiated with UV light. The DNA is isolated and denatured, and the resulting single-stranded DNA is examined by analytical ultracentrifugation. Samples from the normal fibroblasts show a significant reduction in the average molecular weight of the single-stranded DNA after irradiation, but samples from the XPG fibroblasts show no such reduction. Why might this be?

Answer 1

XPG fibroblasts show no reduction in molecular weight after UV irradiation because their nucleotide excision repair mechanism is defective, preventing the removal of thymine dimers and maintaining the distorted DNA structure.

Step-by-step explanation:

The lack of reduction in molecular weight of the single-stranded DNA from XPG fibroblasts indicates that nucleotide excision repair is not occurring, as thymine dimers that distort DNA structure are not being removed.

In healthy individuals, DNA exposed to UV light undergoes a repair process where enzymes involved in nucleotide excision repair mechanism identify and excise thymine dimers—abnormal bonds formed between adjacent thymine nucleotides. These dimers are created when the DNA absorbs UV radiation, leading to disruption in the DNA structure. The excision repair mechanism allows for the removal of these dimers, followed by a restoration of normal DNA structure, resulting in a reduction in the molecular weight of the single-stranded DNA post-irradiation.

Xeroderma pigmentosum (XP) is a condition where patients harbor mutations in genes responsible for nucleotide excision repair. XPG fibroblasts, from patients with the XPG variant of XP, show no reduction in molecular weight after UV irradiation because the repair enzymes are deficient or absent. Consequently, the thymine dimers remain in the DNA, maintaining the distorted structure and not reducing molecular weight.