Nuclear DNA polymerase (DNA pol)

Nuclear DNA polymerases are a group of essential enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, playing a central role in the replication and maintenance of the nuclear genome [1.4.1, 1.4.2]. In humans, this group comprises 14 distinct enzymes (excluding the mitochondrial Pol γ) classified into families A, B, X, and Y, each with specialized roles in high-fidelity replication or various DNA repair pathways [1.4.3, 1.4.5]. The replicative polymerases (α, δ, and ε) are responsible for the bulk of DNA synthesis during the S-phase, while others like Pol β and Pol θ are critical for base excision repair and double-strand break repair, respectively [1.4.1, 1.5.3]. Due to their necessity for cell division, these polymerases are major targets for antimetabolite chemotherapies, such as cytarabine and gemcitabine, which act as nucleoside analogs to induce chain termination [1.3.1, 1.3.4]. Emerging therapeutic strategies focus on the synthetic lethal relationship between specific polymerases, such as Pol θ, and deficiencies in other repair pathways like BRCA1/2, offering a more targeted approach to treating certain cancers [1.1.5, 1.5.1].

Other names

Nuclear DNA-directed DNA polymeraseEukaryotic DNA polymeraseReplicative DNA polymeraseRepair DNA polymerase

Nucleoside analogs act as competitive inhibitors of dNTPs and are incorporated into the DNA strand, causing chain termination or replication fork stalling [1.3.1, 1.3.4]. Small molecule inhibitors like ART558 target the polymerase or helicase domains of specific enzymes like Pol θ to disrupt repair pathways [1.1.5, 1.5.1].