Abstract
The major molecular mode of action of the cytotoxic drug 5-fluorouracil (5-FU) is generally considered to result from thymidylate synthase inhibition. Recent findings relating to the function of the human uracil-5 methyltransferase (U5MT), TRMT2A, and its interaction with 5-FU metabolites incorporated within tRNAs, lead to an additional hypothesis that is proposed here.
Keywords:
5-fluorouracil; 5-methyluridine; DNA break repair; NUD1; RNA methylation; TRMT2A; homologous recombination.
Copyright © 2020 Elsevier Inc. All rights reserved.
MeSH terms
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Survival / drug effects
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Cell Survival / genetics
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DNA Damage
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Fluorouracil / pharmacology*
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Fluorouracil / therapeutic use
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Humans
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Methylation / drug effects
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Neoplasms / drug therapy*
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Neoplasms / genetics
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RNA, Transfer / metabolism
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Recombinational DNA Repair / drug effects*
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Uridine Triphosphate / analogs & derivatives
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Uridine Triphosphate / metabolism
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tRNA Methyltransferases / antagonists & inhibitors*
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tRNA Methyltransferases / metabolism
Substances
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5-fluorouridine 5'-triphosphate
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RNA, Transfer
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TRMT2A protein, human
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tRNA Methyltransferases
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tRNA(uracil-5)-methyltransferase
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Fluorouracil
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Uridine Triphosphate