An 18-year-old man comes to the urgent care clinic due to painful erythema affecting his extremities, trunk, and face. He is vacationing in Florida and spent 5 hours at a Gulf coast beach earlier in the day. The patient did not apply any sunscreen as it was cloudy. The physician explains that cloud cover does not afford a high degree of protection against the sun, especially with prolonged exposure in highly reflective environments like the beach. He is advised to wear protective clothing and apply sunscreen to prevent recurrence. Which of the following is most likely to happen within the patient's skin cells as a result of his exposure?
Show Explanatory Sources
DNA can be damaged by a number of agents, including chemicals, ultraviolet radiation, and ionizing radiation. Ultraviolet rays damage DNA primarily through formation of abnormal covalent bonds between adjacent thymine or cytosine residues (pyrimidine dimers). The presence of pyrimidine dimers interferes with base recognition during transcription and replication, and DNA mutations can result if the damage is not repaired.
Pyrimidine dimers are removed by nucleotide excision repair. In this process, a specific endonuclease complex detects abnormalities in the DNA structure caused by the formation of DNA photoproducts. The endonuclease complex then nicks the damaged strand on both sides of the pyrimidine dimer, and the defective region is excised. DNA polymerase synthesizes new DNA in the place of the damaged DNA, and DNA ligase seals the final remaining nick.
Mutations that impair the components involved in nucleotide excision repair cause xeroderma pigmentosum, a condition characterized by severe photosensitivity and the development of skin cancers at a young age.
(Choice A) Ultraviolet radiation causes the formation of pyrimidine-pyrimidine dimers, not purine-purine dimers.
(Choice B) Exposure to ionizing radiation (x-rays and gamma rays) causes double-strand DNA breaks. The fractured ends can be joined by nonhomologous end joining.
(Choice D) Incorrect base substitution occurs during normal DNA replication and can result in mutations if they are not corrected. DNA mismatch repair in certain prokaryotes is guided by hypermethylation of the parent strand, which helps to identify the non-mutated strand for use as a template.
(Choice E) Deamination of DNA bases (eg, cytosine conversion to uracil, adenine to hypoxanthine) can occur spontaneously or secondary to chemical exposure. These errors are corrected by base excision repair. In this process, abnormal bases are recognized and removed by specific glycosylases without disruption of the phosphodiester backbone. The apurinic and apyrimidinic residues are then removed by specific endonucleases and replaced with the correct base by DNA polymerase.
Educational objective:
Pyrimidine dimers are formed in DNA as a result of ultraviolet light exposure. They are recognized by a specific endonuclease complex that initiates the process of repair by nicking the damaged strand on both sides of the pyrimidine dimer. The damaged segment is then excised, and replacement DNA is synthesized by DNA polymerase.