Target intelligence / Profile preview

DNA polymerase (DNA Pol) (DNA Pol)

Target
DNA Pol
Molecular classification
Enzyme, Transferase, DNA-directed DNA polymerase
01

Overview

DNA polymerase is a fundamental enzyme responsible for the synthesis of DNA molecules from nucleoside triphosphates (StatPearls, 2023). It functions by reading an existing DNA template and catalyzing the addition of complementary nucleotides to the 3' end of a growing DNA strand (UniProt, 2024). In the context of therapeutic intervention, the active site of the replicating DNA polymerase is targeted by various antimetabolites and antiviral agents (PubMed, 2022). These drugs, often nucleoside or nucleotide analogs, mimic natural substrates to inhibit the enzyme's activity or cause premature chain termination, effectively halting cell division or viral replication (NIH, 2023). This mechanism is central to the treatment of numerous cancers and viral infections, such as herpes simplex and HIV (PubChem, 2024). However, the high conservation of DNA polymerases across species and cell types necessitates careful drug design to minimize off-target effects on host mitochondrial DNA or healthy proliferating cells (Wikipedia, 2024). Inhibition of this target can lead to cell cycle arrest and apoptosis, making it a cornerstone of chemotherapy and infectious disease management (StatPearls, 2023). Notable examples include acyclovir for herpesviruses and cytarabine for hematologic malignancies (PubMed, 2022).

Other names
DNA-directed DNA polymeraseDNA nucleotidyltransferaseReplicating DNA polymeraseDNA polymerase active site
02

Mechanism of action

Inhibition of DNA synthesis through competitive binding at the active site or incorporation into the growing DNA strand leading to chain termination (StatPearls, 2023; NIH, 2023).

03

Biological functions

DNA replicationDNA repairCell proliferationGenome maintenance
04

Disease associations

CancerViral infectionBacterial infection
05

Safety considerations

MyelosuppressionNephrotoxicityMitochondrial toxicity (Pol gamma inhibition)Gastrointestinal toxicityNeurotoxicity
06

Interacting drugs

Acyclovir

8 more in the full profile.

07

Biomarkers

Ki-67Proliferating Cell Nuclear Antigen (PCNA)Viral loadDNA polymerase activity

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