On a New Proposed Mechanism of 5-Fluorouracil-Mediated Cytotoxicity

Trends Cancer. 2020 May;6(5):365-368. doi: 10.1016/j.trecan.2020.02.009. Epub 2020 Mar 13.

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.

MeSH terms

  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • DNA Damage
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use
  • Humans
  • Methylation / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • RNA, Transfer / metabolism
  • Recombinational DNA Repair / drug effects*
  • Uridine Triphosphate / analogs & derivatives
  • Uridine Triphosphate / metabolism
  • tRNA Methyltransferases / antagonists & inhibitors*
  • tRNA Methyltransferases / metabolism

Substances

  • 5-fluorouridine 5'-triphosphate
  • RNA, Transfer
  • TRMT2A protein, human
  • tRNA Methyltransferases
  • tRNA(uracil-5)-methyltransferase
  • Fluorouracil
  • Uridine Triphosphate