Other replicative DNA polymerases

Other replicative DNA polymerases is a collective classification, primarily used in pharmacological databases like ChEMBL, to refer to the processive eukaryotic DNA polymerases, specifically DNA polymerase delta (Pol δ) and DNA polymerase epsilon (Pol ε). These enzymes are distinct from DNA polymerase alpha-primase, as they are responsible for the bulk of genomic DNA synthesis on the lagging and leading strands, respectively. They are characterized by high processivity, facilitated by their interaction with the Proliferating Cell Nuclear Antigen (PCNA) sliding clamp, and high fidelity due to their intrinsic 3'-5' exonuclease proofreading activity. Mutations in the catalytic subunits of these polymerases (POLE and POLD1) are linked to hypermutated and ultramutated cancer phenotypes, particularly in colorectal and endometrial cancers, making them significant biomarkers for predicting response to immune checkpoint inhibitors. Pharmacologically, these polymerases are targeted by various nucleoside analogs and antimetabolites that act as competitive inhibitors or chain terminators to disrupt DNA replication and induce apoptosis in rapidly dividing cells.

Other names

DNA polymerase deltaDNA polymerase epsilonProcessive DNA polymerasesB-family DNA polymerasesPOLDPOLE

Inhibition of DNA synthesis through competitive inhibition with natural deoxynucleoside triphosphates (dNTPs) or by acting as DNA chain terminators upon incorporation into the nascent DNA strand.