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 synthesizing new DNA strands by adding nucleotides to a template, a process essential for both DNA replication and repair [1][2]. In the context of the DNA replication machinery, it works in coordination with other proteins like helicases, primases, and sliding clamps to ensure genomic integrity during the cell cycle [2]. Because rapid cell division is a hallmark of both cancer and viral replication, DNA polymerases are critical therapeutic targets [3]. Antiviral drugs, such as acyclovir, often act as nucleoside analogs that cause premature chain termination once incorporated into the viral DNA strand by the viral polymerase [4]. Similarly, chemotherapeutic agents like cytarabine inhibit human DNA polymerases to halt the proliferation of malignant cells in leukemias and solid tumors [5]. However, targeting these enzymes can lead to significant side effects, such as myelosuppression, due to the unintended inhibition of DNA synthesis in healthy, rapidly dividing host cells [5].

Other names
DNA-directed DNA polymeraseDNA replication machineryReplisomeDNA-dependent DNA polymeraseDNA replication complex
02

Mechanism of action

Inhibition of DNA synthesis through competitive binding with endogenous deoxyribonucleotides at the polymerase active site, leading to DNA chain termination or the formation of defective DNA strands that trigger apoptosis.

03

Biological functions

DNA replicationDNA repairGenome maintenanceCell cycle progression
04

Disease associations

CancerViral infectionBacterial infection
05

Safety considerations

MyelosuppressionNephrotoxicityNeurotoxicityGastrointestinal toxicityPotential mutagenicity
06

Interacting drugs

Acyclovir

11 more in the full profile.

07

Biomarkers

POLE mutation statusPOLD1 mutation statusKi-67 expression levelsProliferating cell nuclear antigen (PCNA) levels

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