Human cellular DNA polymerase (DNA Pol)

Human cellular DNA polymerases are a diverse group of enzymes responsible for synthesizing DNA molecules from nucleoside triphosphates (UniProt, 2024). These enzymes are categorized into several families (A, B, X, Y, and others) based on their sequence homology and functional roles, including high-fidelity genomic replication (Pol delta and epsilon), DNA repair (Pol beta), and mitochondrial DNA maintenance (Pol gamma) (PubMed, PMID: 27131021). In the context of oncology, certain polymerases like Pol alpha, delta, and epsilon are primary targets for antimetabolite chemotherapy drugs, which act as nucleoside analogs to disrupt DNA synthesis and induce apoptosis in rapidly dividing cancer cells (StatPearls, 2023). Conversely, mutations in the proofreading domains of Pol epsilon (POLE) and Pol delta (POLD1) are recognized as drivers of hypermutated phenotypes in colorectal and endometrial cancers, serving as critical biomarkers for immunotherapy response (NIH, 2022). Furthermore, while many antiviral drugs are designed to target viral polymerases, their unintended interaction with human cellular polymerases—particularly the mitochondrial Pol gamma—can lead to significant clinical toxicities such as lactic acidosis and organ failure (PubChem, 2024). Understanding the specificity and functional diversity of these enzymes is essential for developing more selective therapeutic agents with improved safety profiles.

Other names

DNA-directed DNA polymeraseDeoxyribonucleic acid polymeraseCellular DNA polymerase

Inhibition of DNA synthesis through competitive binding with natural deoxynucleoside triphosphates (dNTPs) or via incorporation into the growing DNA strand leading to chain termination or stalling of the replication fork (PubMed, PMID: 11596676).