Thymidylate synthase and Deoxyribonucleic acid (TYMS; DNA)

Thymidylate synthase (TS) is a critical enzyme (EC 2.1.1.45) that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), providing the sole de novo source of thymidylate for DNA synthesis (UniProt P04818). DNA serves as the primary repository of genetic information and is a direct target for antimetabolites that mimic natural nucleotides (NCBI, PMC3685369). Drugs like 5-fluorouracil (5-FU) target this system by forming a stable ternary complex with TS and its cofactor, thereby inhibiting dTMP production, while its metabolites are also incorporated into DNA, leading to lethal strand breaks (StatPearls, Fluorouracil). This dual mechanism effectively halts the cell cycle in the S-phase and induces apoptosis, particularly in rapidly proliferating malignant cells (PubMed, 15151916). Clinical use of these inhibitors is widespread in treating solid tumors, including colorectal and breast cancers, though efficacy is often limited by the upregulation of TS expression or metabolic degradation of the drug (NIH, Cancer.gov).

Other names

TYMSThymidylate synthetaseDNADeoxyribonucleic acidTSDNA and thymidylate synthase

Inhibition of thymidylate synthase (TYMS) prevents the synthesis of dTMP, leading to thymineless death, while the incorporation of fraudulent nucleotides into DNA causes genomic instability and apoptosis (StatPearls, Fluorouracil; PubMed, 15151916).