DNA polymerase (replicative) (DNA Pol)

DNA polymerases are essential enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, serving as the primary engines of genomic replication (NCBI, 2023). Replicative DNA polymerases, such as Pol alpha, delta, and epsilon in eukaryotes, are characterized by high fidelity and processivity, ensuring the accurate transmission of genetic information during the S-phase of the cell cycle (Nature Reviews Molecular Cell Biology, 2016). These enzymes are critical therapeutic targets in oncology and infectious diseases because rapidly dividing cancer cells and replicating pathogens are highly dependent on efficient DNA synthesis (Journal of Biological Chemistry, 2010). Antineoplastic agents like cytarabine and gemcitabine act as antimetabolites that inhibit these polymerases or cause DNA chain termination, leading to cell death (StatPearls, 2023). Similarly, many antiviral drugs, such as acyclovir, selectively target viral DNA polymerases to halt the progression of infections like herpes simplex virus (Clinical Microbiology Reviews, 2003). Mutations in replicative polymerases, particularly POLE and POLD1, are also used as biomarkers to identify ultramutated tumors that may respond well to immunotherapy (Journal of Pathology, 2017).

Other names

DNA-directed DNA polymeraseReplicative DNA polymeraseDNA nucleotidyltransferase (DNA-directed)DNA polymerase alphaDNA polymerase deltaDNA polymerase epsilon

Inhibition of DNA synthesis through competitive binding with deoxyribonucleotide triphosphates (dNTPs) or via incorporation into the DNA strand leading to premature chain termination (StatPearls, 2023).