Target intelligence / Profile preview

Cellular DNA and RNA polymerases (DNA/RNA Pol)

Target
DNA/RNA Pol
Molecular classification
Enzyme, Polymerase, Transferase
01

Overview

Cellular DNA and RNA polymerases are a broad class of enzymes essential for the synthesis of nucleic acids, encompassing DNA-directed DNA polymerases and DNA-directed RNA polymerases. DNA polymerases, such as Pol alpha, delta, and epsilon, are responsible for genome replication and repair, ensuring genetic stability across cell generations [Hübscher et al., 2002]. RNA polymerases, including Pol I, II, and III, catalyze the transcription of DNA into various RNA species required for protein synthesis and cellular regulation [Cramer, 2019]. These enzymes are critical therapeutic targets in oncology, where inhibitors like cytarabine and gemcitabine act as antimetabolites to disrupt DNA synthesis in rapidly dividing cancer cells [Kaufman et al., 1991]. Additionally, novel inhibitors like CX-5461 specifically target RNA polymerase I to treat advanced hematologic and solid tumors [Drygin et al., 2011]. However, because these enzymes are fundamental to all cellular life, drugs targeting them often carry significant safety concerns, including myelosuppression and systemic toxicity, due to their impact on healthy proliferating tissues [StatPearls, 2023].

Other names
DNA-directed DNA polymeraseDNA-directed RNA polymeraseDNA nucleotidyltransferaseRNA nucleotidyltransferaseDNA replicaseRNA transcriptase
02

Mechanism of action

Competitive inhibition of nucleotide binding, DNA chain termination following incorporation, and template blocking via DNA intercalation.

03

Biological functions

DNA replicationDNA repairTranscriptionMitochondrial genome maintenanceCell cycle progression
04

Disease associations

CancerViral infectionAutoimmune diseaseGenetic instability disorders
05

Safety considerations

MyelosuppressionGastrointestinal toxicity (mucositis)GenotoxicityHepatotoxicityNephrotoxicityAlopecia
06

Interacting drugs

Cytarabine

7 more in the full profile.

07

Biomarkers

Ki-67 (proliferation marker)POLR2A expressionPCNA (Proliferating Cell Nuclear Antigen)Microsatellite instability (MSI)

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