Replicative DNA polymerase active site and nascent DNA chain (DNA Pol (active site))

The replicative DNA polymerase active site and nascent DNA chain constitute the catalytic machinery essential for genome duplication and maintenance (Nature Education, 2014). This target involves the precise coordination between the polymerase enzyme, the template DNA, and the growing nascent strand, where deoxynucleoside triphosphates (dNTPs) are sequentially added (Journal of Biological Chemistry, 2020). In clinical practice, this site is the primary target for a wide array of antiviral and antineoplastic agents, most notably nucleoside and nucleotide analogs (StatPearls, 2023). These drugs function by mimicking natural substrates and competing for entry into the active site; once incorporated into the nascent DNA chain, they typically prevent further elongation due to the absence of a 3'-hydroxyl group or through steric hindrance (NIH/PubChem, 2024). This inhibition effectively halts the replication of viral genomes or the division of rapidly proliferating cancer cells, making it a cornerstone of modern chemotherapy and infectious disease management (PubMed, 2022).

Other names

DNA polymerase catalytic centerDNA polymerase-DNA complexPrimer-template junctionDNA polymerase active site

Competitive inhibition of dNTP binding and incorporation into the nascent DNA chain, leading to obligate or non-obligate chain termination.