DNA synthesis enzyme

DNA synthesis enzymes comprise a set of molecular machines responsible for the replication and repair of DNA, most notably during cell division. The two principal therapeutic targets in chemotherapy are DNA polymerases, which catalyze the addition of nucleotides in a template-directed manner, and thymidylate synthase, which is essential for de novo pyrimidine nucleotide biosynthesis. Pharmacologic inhibition of these enzymes (by agents such as 5-fluorouracil, methotrexate, and cytarabine) blocks DNA replication, induces cell cycle arrest, and triggers apoptosis, especially in rapidly proliferating cancer cells, making them central nodes of action for chemotherapeutic regimens such as NUFOX. Other DNA synthesis enzymes, such as DNA topoisomerases, are also targeted to induce DNA damage through strand breaks. However, resistance and toxicity stemming from effects on normal proliferative cells are major challenges in their clinical use.

Other names

DNA synthesis proteinDNA replication enzymeDNA polymeraseThymidylate synthase (TS)DNA topoisomeraseDNA replication machinery

Inhibition of dTMP synthesis (TS inhibitors like 5FU, methotrexate); Direct inhibition of DNA polymerase activity (nucleoside analogs, cytarabine); DNA damage induction (alkylating agents like temozolomide); DNA topoisomerase poisoning (strand breaks, e.g., irinotecan, doxorubicin); Incorporation of faulty nucleotides (purine/pyrimidine analogs, 6-MP, 6-TG).