title: Participation of DNA repair in the response to 5-fluorouracil.
abstract: The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anticancer treatments.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA. wyatt@sccp.sc.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Wyatt
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D005472:Fluorouracil / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000964:Antimetabolites, Antineoplastic; D004247:DNA; D045647:DNA Glycosylases; D045643:DNA Repair Enzymes; D005472:Fluorouracil