A 6-year-old boy is brought to the office due to a persistent facial ulcer for the past 2 months. His mother reports that the patient has extreme sensitivity to sunlight and has developed freckles on his face, neck, and limbs since infancy. On physical examination, the skin in sun-exposed areas is dry and rough with numerous freckles and erythematous macules. There is an ulcerated plaque on the left face; a biopsy reveals squamous cell carcinoma. Further testing leads to a diagnosis of xeroderma pigmentosum. A defect in which of the following enzymes is most likely causing this patient's condition?

Question

A 6-year-old boy is brought to the office due to a persistent facial ulcer for the past 2 months.  His mother reports that the patient has extreme sensitivity to sunlight and has developed freckles on his face, neck, and limbs since infancy.  On physical examination, the skin in sun-exposed areas is dry and rough with numerous freckles and erythematous macules.  There is an ulcerated plaque on the left face; a biopsy reveals squamous cell carcinoma.  Further testing leads to a diagnosis of xeroderma pigmentosum.  A defect in which of the following enzymes is most likely causing this patient's condition?

Quizplus · Accepted Answer

11ec160b_377b_46df_9249_9531cdc2ed85_MD0001_00 This boy with severe photosensitivity, poikiloderma, hyperpigmentation in sun-exposed areas, and squamous cell carcinoma of the skin has xeroderma pigmentosum, an autosomal recessive disorder characterized by defects in nucleotide excision repair. DNA can be damaged by ultraviolet rays, leading to formation of thymine dimers between 2 adjacent thymine residues. These thymine dimers are repaired by UV-specific endonuclease, an enzyme that is frequently deficient in patients with xeroderma pigmentosum. This enzyme recognizes distortions in the structure of DNA caused by thymine dimers and subsequently excises stretches of single-stranded DNA that contain these defects. The gap created following this excision is then filled by DNA polymerase, which uses the opposite DNA strand as a template. The new strand of DNA is then joined on both ends to the existing DNA by the enzyme ligase. (Choice A) 3'→5' exonuclease activity describes the "proofreading" ability of DNA polymerase. This ability allows for the recognition and repair of mismatched bases during DNA replication. Hereditary nonpolyposis colon cancer is associated with DNA mismatch repair gene mutations. (Choice B) DNA ligase is responsible for creating a phosphodiester linkage between the phosphate group of the 5' end of a DNA fragment and the hydroxyl group of the 3' end. DNA ligase is particularly active in joining the Okazaki fragments created during discontinuous replication of the lagging strand. (Choice D) Helicases are responsible for unwinding and separating double-stranded DNA into single-stranded DNA in preparation for DNA replication. (Choice E) Topoisomerase enzymes relieve DNA supercoiling produced during unwinding and separation by helicase. Prokaryotic topoisomerase II (DNA gyrase) is inhibited by fluoroquinolone antibiotics, whereas eukaryotic topoisomerase II is inhibited by the anticancer drug etoposide. Educational objective: Xeroderma pigmentosum is an autosomal recessive disorder characterized by defective nucleotide excision repair often caused by a deficiency in UV-specific endonuclease. Affected children usually have severe photosensitivity, hyperpigmentation in sun-exposed areas, and a greatly increased risk for skin cancer. __________ References: Xeroderma pigmentosum. (http://www.ncbi.nlm.nih.gov/pubmed/22044607)

A 6-Year-Old Boy Is Brought to the Office Due to a Persistent