Xeroderma Pigmentosum

Xeroderma pigmentosum is a disease that illustrates what happens when DNA repair does not work properly. The disease is characterized by abnormal skin pigmentation that resembles freckles and sensitivity to sunlight. Patients suffering from the disease also have a strong predisposition to skin cancer.

In order to understand the disease, let’s review some concepts we covered when we talked about DNA mutations and DNA repair. First, sunlight includes a UV component, which is absorbed by pyrimidine bases and causes the formation of chemical bonds between adjacent pyrimidine molecules. This creates molecules known as pyrimidine dimers that distort the DNA helix and often block replication.

Such pyrimidine dimers can be corrected by nucleotide-excision repair, a DNA repair mechanism that is able to remove these distorted parts of DNA and resynthesize the missing strand. It uses a complex of enzymes that finds the distorted part of the DNA and separates its two strands. The damaged part of the strand is removed, and the gap is filled in by DNA polymerase. DNA ligase then again joins the newly synthesized nucleotides with the undamaged DNA strands. People suffering from the disease, however, have a defect in the mechanism, which means that many pyrimidine dimers are not removed and for that reason may lead to cancer.

References:
Pierce, B. A. (2019). Genetics: A Conceptual Approach (Seventh ed.). W. H. Freeman.
Snustad, D. P., & Simmons, M. J. (2012). Principles of Genetics. Wiley.