DNA polymerase and nascent DNA (DNA Pol-DNA complex)

The DNA polymerase and nascent DNA complex is the fundamental machinery responsible for the synthesis of new genetic material during cell division and viral replication. DNA polymerases are enzymes that read a template strand and catalyze the addition of complementary deoxynucleotide triphosphates (dNTPs) to the 3' end of a growing, or nascent, DNA chain (Kornberg & Baker, DNA Replication, 1992). This complex is a primary target for a wide range of therapeutic agents, particularly in the treatment of viral infections and cancer. Antiviral drugs such as acyclovir and tenofovir are nucleoside/nucleotide analogs that are phosphorylated by cellular or viral kinases and then incorporated into the nascent DNA by the polymerase; because these analogs lack a 3'-hydroxyl group, they cause premature chain termination (PubMed: 16412911). In oncology, cytostatic agents like cytarabine and gemcitabine target human DNA polymerases to inhibit the rapid DNA synthesis required for tumor cell proliferation (StatPearls, 2023). Therapeutic challenges include the potential for off-target inhibition of host mitochondrial DNA polymerase gamma, which can lead to organ toxicity, and the development of drug resistance through mutations in the polymerase gene (PubMed: 10835501).

Other names

DNA polymerase-template-primer complexReplication fork complexNascent DNA chainDNA polymerase-DNA complex

Nucleoside and nucleotide analogs act as competitive inhibitors of natural dNTPs and, upon incorporation into the nascent DNA strand by DNA polymerase, function as chain terminators that prevent further phosphodiester bond formation (StatPearls, 2023; PubMed: 16412911).