Cell Death Caused by the Anti-Cancer Drug Methotrexate: Does ADP-Ribosyl Transferase Have a Role to Play?

Thymidylate residues required for cellular DNA synthesis are obtained exogenously via the salvage pathway and/or are synthesised de novo via dUMP in a reaction catalysed by thymidylate synthase (dUMP → dTMP). The thymidine monophosphate can then be phosphorylated by kinases to dTDP and dTTP before being incorporated into DNA.