Target intelligence / Profile preview

DNA-directed RNA polymerase (RNAP) and DNA-directed DNA polymerase (DNAP) (RNAP / DNAP)

Target
RNAP / DNAP
Molecular classification
Enzyme, Transferase, Nucleic acid polymerase
01

Overview

DNA-dependent RNA polymerase (RNAP) and DNA polymerase (DNAP) are essential enzymes that catalyze the synthesis of RNA and DNA, respectively, using a DNA template (Nature Education, 2014). RNAP is responsible for transcription, the process by which genetic information is transferred from DNA to RNA, which is vital for protein synthesis and cellular regulation (StatPearls, 2023). DNAP is the primary enzyme involved in DNA replication and repair, ensuring the accurate transmission of genetic material during cell division (Nature Education, 2014). These enzymes are prominent therapeutic targets in various diseases; for example, bacterial RNAPs are targeted by the rifamycin class of antibiotics to treat infections like tuberculosis (StatPearls, 2023). Viral DNAPs are frequently targeted by nucleoside analogs, such as acyclovir, to inhibit the replication of viruses like Herpes Simplex (StatPearls, 2022). In oncology, human DNA polymerases are targeted by antimetabolite drugs like cytarabine to halt the proliferation of cancer cells (Frontiers in Molecular Biosciences, 2021). Because these enzymes are fundamental to life, drug development often focuses on achieving selectivity for microbial or viral versions over human counterparts to minimize toxicity (NIH, 2023).

Other names
RNAPDNAPDNA-directed RNA polymeraseDNA-directed DNA polymeraseRNA polymeraseDNA polymeraseTranscriptaseReplicasePrimPol
02

Mechanism of action

Inhibition of nucleic acid synthesis by blocking the elongation of the RNA or DNA chain, often through competitive binding at the active site or by acting as a chain terminator after incorporation into the nascent strand.

03

Biological functions

TranscriptionDNA replicationDNA repairGene expressionRNA synthesisDNA synthesis
04

Disease associations

InfectionCancerGenetic disordersViral replicationBacterial pathogenesis
05

Safety considerations

Mitochondrial toxicity (due to inhibition of POLG)MyelosuppressionNephrotoxicityHepatotoxicityDevelopment of antimicrobial resistance
06

Interacting drugs

Rifampicin

8 more in the full profile.

07

Biomarkers

Viral load (e.g., HBV DNA, HSV DNA)Bacterial culture and sensitivityPolymerase gene mutations (e.g., rpoB for rifampicin resistance)Microsatellite instability (MSI)

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