Target intelligence / Profile preview

DNA and RNA polymerase and nucleotide-processing enzyme

Molecular classification
Enzyme, Polymerase, Nuclease (for nucleotide-processing enzymes such as endonucleases/exonucleases), Transcription factor (for associated regulatory proteins, but not the enzymes themselves)
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Overview

DNA and RNA polymerases, along with related nucleotide-processing enzymes (including nucleases), are a superfamily of enzymes essential for nucleic acid metabolism. DNA polymerases catalyze the synthesis of DNA from deoxynucleoside triphosphates using a DNA template, playing critical roles in DNA replication and repair. RNA polymerases catalyze the transcription of DNA to synthesize RNA, regulating gene expression and enabling cellular function. Nucleotide-processing enzymes such as nucleases cleave nucleic acids for repair, recombination, or degradation. These targets are highly conserved, essential for cell survival, and key regulators of biological information flow. They are prominent therapeutic targets for antiviral, anticancer, and antimicrobial agents due to their indispensable roles in cell division and viral replication. Targeting these enzymes, however, can present significant safety and selectivity challenges, since inhibition in host tissues can disrupt normal cell function and lead to toxicity.

Other names
DNA polymeraseRNA polymerasenucleic acid polymerasenucleotide-processing enzymeRNA transcriptasereverse transcriptaseterminal deoxynucleotidyl transferasenucleases
02

Mechanism of action

Competitive inhibition by nucleoside/nucleotide analogs, which are incorporated in place of natural nucleotides and terminate chain elongation or introduce mutations; Allosteric inhibition of enzyme active site; Inhibition of binding to DNA or template RNA; Interference with enzyme-substrate recognition

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Biological functions

DNA replicationTranscriptionDNA repairRNA processingGene expression regulationCell proliferationCell cycle progressionApoptosis (via DNA repair/signaling pathways)
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Disease associations

CancerViral infectionMitochondrial disordersGenetic disease (due to polymerase/nuclease mutations)Other (including autoimmune, metabolic, and neurodegenerative disease via error accumulation or altered gene expression)
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Safety considerations

Cytotoxicity due to inhibition of normal host DNA and RNA polymerasesOff-target effects leading to bone marrow suppression, neurotoxicity, or mitochondrial toxicityDrug resistance via polymerase mutationsPotential teratogenicity (inhibiting polymerase function in dividing fetal cells)Cumulative mutagenesis with some agents
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Interacting drugs

Nucleoside analogs (e.g., zidovudine, lamivudine, remdesivir, cytarabine, gemcitabine, acyclovir)

5 more in the full profile.

07

Biomarkers

Expression levels of DNA/RNA polymerase (especially POLG, POLD, POLA, POLB, POLR2A, etc., in tumors and viral infections)Polymerase mutations (e.g., POLG mutations in mitochondrial disorders, POLQ in cancer)Viral DNA/RNA load (as readout of polymerase activity in infection)dNTP/rNTP pool levels in some cancers or viral infections

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