Mammalian DNA polymerase (DNA pol)

Mammalian DNA polymerases are a diverse family of enzymes responsible for the synthesis of DNA molecules from nucleoside triphosphates, playing a central role in genome replication, maintenance, and repair [1]. These enzymes are classified into several families (A, B, X, Y, and others) based on their sequence homology and functional specialization, with Pol alpha, delta, and epsilon serving as the primary replicative polymerases in the nucleus, while Pol gamma handles mitochondrial DNA synthesis [1][2]. In clinical practice, these polymerases are major targets for antimetabolite drugs, particularly in the treatment of hematologic malignancies and solid tumors [3]. Nucleoside analogs like cytarabine and gemcitabine function by mimicking natural substrates, leading to competitive inhibition or DNA chain termination upon incorporation, which triggers cell cycle arrest and apoptosis [3][5]. Mutations in specific polymerases, such as POLE and POLD1, are recognized as critical drivers and biomarkers in certain cancers, often leading to a hypermutated phenotype [4]. Despite their therapeutic utility, the inhibition of these enzymes in healthy, rapidly dividing tissues results in characteristic toxicities, including myelosuppression and gastrointestinal distress [5].

Other names

DNA-directed DNA polymerasePol alphaPol betaPol gammaPol deltaPol epsilonPol zetaPol etaPol iotaPol kappaPol lambdaPol muPol nuRev1

Inhibition of DNA synthesis through competitive binding with natural deoxyribonucleotide triphosphates (dNTPs) or induction of DNA chain termination following incorporation into the nascent DNA strand.