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DNA-directed DNA polymerase and DNA-directed RNA polymerase (DNA polymerase (for DNA-directed DNA polymerase), RNA polymerase (for DNA-directed RNA polymerase))

Target
DNA polymerase (for DNA-directed DNA polymerase), RNA polymerase (for DNA-directed RNA polymerase)
Molecular classification
Enzyme, Polymerase
01

Overview

DNA and RNA polymerases are families of enzymes that catalyze the synthesis of DNA and RNA, respectively. **DNA polymerase** is central to the accurate replication and repair of DNA, using an existing DNA strand as a template to assemble a new complementary strand during the S phase of the cell cycle. It requires a primer and proofreads for errors, ensuring fidelity in genetic transmission[1][2]. **RNA polymerase** synthesizes RNA from a DNA template in the process of transcription, a crucial step in gene expression. Unlike DNA polymerase, RNA polymerase does not require a primer and is involved in multiple stages: initiation (binding to promoter), elongation (synthesizing the RNA strand), and termination (releasing the transcript)[3][4][5][6]. These enzymes are found in all domains of life, and viral polymerases demonstrate additional diversity, such as RNA-dependent RNA polymerases and reverse transcriptases[7]. Both DNA and RNA polymerases are validated therapeutic targets for cancer, infection, and genetic diseases, but the term "RNA/DNA Polymerases" is overly broad, as it groups functionally and structurally distinct enzymes under a generic label, which can lead to ambiguity in drug development and clinical contexts.

Other names
DNA-dependent DNA polymeraseDNA-dependent RNA polymeraseDNA polymeraseRNA polymeraseRNAPDNA replicaseDNA-directed RNA polymerase
02

Mechanism of action

Inhibition of polymerase active site (competitive or non-competitive) Chain termination by incorporation of analogs Allosteric inhibition Blocking initiation or elongation of nucleic acid synthesis

03

Biological functions

DNA replication (DNA polymerase)DNA repair (DNA polymerase)Transcription (RNA polymerase)Gene expression regulation (RNA polymerase)
04

Disease associations

Cancer (mutations or dysregulation of DNA or RNA polymerases can lead to oncogenesis or alter drug response)Infection (target for antiviral and antibacterial drugs)Genetic diseases (defects in replication/repair polymerases)Other (neurodegenerative disease via genome instability, immunodeficiency syndromes)
05

Safety considerations

Off-target toxicity in rapidly dividing normal cells (for DNA polymerase inhibitors)Mitochondrial toxicity (nucleoside analogs can inhibit mitochondrial DNA polymerase γ)Immune suppression or mutagenesisViral resistance (selection of resistant polymerase mutants)
06

Interacting drugs

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

3 more in the full profile.

07

Biomarkers

Polymerase mutations (e.g., POLG in mitochondrial diseases, POLRMT for sensitivity to antivirals)Expression levels of RNA polymerase II as proliferation index in some tumors

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