A 56-year-old man comes to the office due to difficulty swallowing for the past several months. He has the most trouble with solid foods and says, "They seem to get stuck in my throat if I don't chew a lot." The patient has no chest pain or heartburn and has lost 4.5 kg (10 lb) in the last 3 months. He has been an avid hunter for many years and frequently cures the meat he eats with sodium nitrite. Physical examination is unremarkable. Endoscopy shows an ulcerated mass in the distal third of the esophagus, and biopsy samples are obtained from the mass and adjacent normal mucosa. Analysis of the samples shows accelerated cytosine deamination of chromosomal DNA in both normal and malignant epithelial cells. This damage is most likely to be repaired through which of the following enzymatic sequences?

Question

A 56-year-old man comes to the office due to difficulty swallowing for the past several months.  He has the most trouble with solid foods and says, "They seem to get stuck in my throat if I don't chew a lot."  The patient has no chest pain or heartburn and has lost 4.5 kg (10 lb) in the last 3 months.  He has been an avid hunter for many years and frequently cures the meat he eats with sodium nitrite.  Physical examination is unremarkable.  Endoscopy shows an ulcerated mass in the distal third of the esophagus, and biopsy samples are obtained from the mass and adjacent normal mucosa.  Analysis of the samples shows accelerated cytosine deamination of chromosomal DNA in both normal and malignant epithelial cells.  This damage is most likely to be repaired through which of the following enzymatic sequences?

Quizplus · Accepted Answer

11ec160b_3764_6449_9249_d10f8204d028_MD0001_00 Base excision repair is responsible for repairing various non-bulky DNA base alterations, including depurination, alkylation, oxidation, and deamination. Excessive consumption of dietary nitrites can promote the deamination of cytosine, adenine, and guanine to form uracil, hypoxanthine, and xanthine, respectively. If these abnormal bases are not removed and replaced with the correct base, DNA mutations and carcinogenesis may result. Base excision repair (not to be confused with nucleotide excision repair or mismatch repair) begins with recognition of abnormal bases by specific glycosylases. These cleave the altered DNA bases from the parent DNA molecule, leaving an empty sugar-phosphate site called an apurinic/apyrimidinic site (AP). An endonuclease then cleaves the 5' end of the AP site before a lyase (or phosphodiesterase) enzyme subsequently completes extraction of the AP site from the DNA molecule by removing the remaining sugar-phosphate group. DNA polymerase then fills the gap with the correct sugar-phosphate base, and the final nick is sealed by ligase. Educational objective: Base excision repair is used to correct single-base DNA defects induced spontaneously or by exogenous chemicals. In this process, glycosylases remove the defective base, and the corresponding empty sugar-phosphate site is cleaved and removed by the action of endonuclease and lyase. DNA polymerase then replaces the missing nucleotide, and ligase seals the final remaining nick. __________ References: Overview of base excision repair biochemistry. (http://www.ncbi.nlm.nih.gov/pubmed/22122461)

A 56-Year-Old Man Comes to the Office Due to Difficulty