Replicative DNA polymerase (DNA Pol) (DNA Pol)

Replicative DNA polymerases are specialized enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, ensuring the accurate transmission of genetic information during cell division (Source: StatPearls). In eukaryotic cells, the primary replicative polymerases include DNA polymerase alpha (Pol α), delta (Pol δ), and epsilon (Pol ε), which function in a highly coordinated complex at the replication fork (Source: UniProt). Pol α initiates synthesis, while Pol δ and Pol ε are responsible for the bulk of lagging and leading strand synthesis, respectively, often utilizing 3'-5' exonuclease activity for proofreading (Source: Nature Reviews Molecular Cell Biology). Dysregulation or mutations in these polymerases, particularly in the proofreading domains of POLE and POLD1, are strongly associated with high tumor mutational burden and various hereditary cancer syndromes (Source: PubMed, PMID: 23447401). Consequently, these enzymes are major targets for anti-cancer therapy; nucleoside analogs like cytarabine and gemcitabine inhibit replication by competing with natural nucleotides or causing premature chain termination (Source: PubChem). Furthermore, the structural differences between human and microbial replicative polymerases allow for the development of selective antiviral and antibacterial drugs that disrupt pathogen genome replication without harming the host (Source: Microbiology and Molecular Biology Reviews).

Other names

DNA-directed DNA polymerase (Source: UniProt)DNA nucleotidyltransferase (Source: UniProt)DNA polymerase alpha (Source: UniProt)DNA polymerase delta (Source: UniProt)DNA polymerase epsilon (Source: UniProt)

Inhibition of DNA synthesis through competitive binding with dNTPs, incorporation into DNA leading to chain termination, or stalling of the replication fork (Source: PubChem).