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  • Title: Mechanisms of excision of 5-fluorouracil by uracil DNA glycosylase in normal human cells.
    Author: Mauro DJ, De Riel JK, Tallarida RJ, Sirover MA.
    Journal: Mol Pharmacol; 1993 Jun; 43(6):854-7. PubMed ID: 8316218.
    Abstract:
    Recent evidence indicates that 5-fluorouracil (5-FlUra) is incorporated into DNA and is removed by the DNA repair enzyme uracil DNA glycosylase. Synthetic oligonucleotides containing either a single uracil or 5-FlUra residue were constructed to examine the mechanisms by which human cells remove 5-FlUra from DNA. The human uracil DNA glycosylase excised uracil in a manner similar to that observed for the bacterial enzyme. In contrast, a significant difference was observed in their abilities to remove 5-FlUra. In particular, both the bacterial and normal human enzymes displayed 13-17-fold increases in their apparent Km values but the apparent Vmax values remained virtually constant. These results demonstrate that normal human cells possess a defined capacity to remove 5-FlUra incorporated into DNA. However, specific kinetic differences may exist that affect their capacity to remove 5-FlUra formed in DNA after treatment with this cancer chemotherapeutic agent.
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