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DNA polymerase, Ribonucleotide reductase

Molecular classification
Enzyme
01

Overview

DNA polymerases are enzymes that catalyze the synthesis of DNA molecules from deoxyribonucleotide triphosphates, essential for DNA replication and repair. There are several families of DNA polymerases in both prokaryotes and eukaryotes, each with specific roles in genome maintenance. Inhibitors of DNA polymerase are used as chemotherapeutic and antiviral agents, exploiting their central role in nucleic acid synthesis[8]. Ribonucleotide reductase is the rate-limiting enzyme for de novo synthesis of deoxyribonucleotides from ribonucleotides. This conversion is essential for DNA replication and repair. The enzyme is regulated tightly at the transcriptional, allosteric, and post-translational levels, reflecting its central importance in cell proliferation and genomic stability. RNR is a validated therapeutic target in cancer, with several clinical inhibitors that impair tumor cell division[1][5][6][2].

Other names
DNA-directed DNA polymerasepolymerase (DNA)DNA-dependent DNA polymeraseribonucleoside diphosphate reductaseribonucleotide reductase large subunit (RRM1)ribonucleotide reductase small subunit (RRM2/RRM2B)
02

Mechanism of action

Inhibition of DNA polymerase activity, blocking DNA elongation, chain termination, increased DNA damage in cancer cells or viruses[8]. Inhibition of deoxyribonucleotide formation by RNR, leading to depletion of dNTP pools, impaired DNA synthesis and repair, S-phase arrest, and cell death[6][2][4].

03

Biological functions

DNA synthesisDNA replicationDNA repairDeoxyribonucleotide synthesisDNA precursor biosynthesisCell proliferationGenome maintenance
04

Disease associations

CancerViral infectionOther (e.g., some rare genetic diseases)Infection (including viral and bacterial replication)
05

Safety considerations

MyelosuppressionOff-target toxicityDrug resistanceMitochondrial toxicity for some antivirals[8]Mutation rate/genomic instability if pools are imbalanced[6][4]
06

Interacting drugs

Nucleoside analogs

9 more in the full profile.

07

Biomarkers

Expression levels/mutations in DNA polymerases (e.g., POL genes) can be prognostic in some cancers and are used to predict viral drug susceptibility.SLFN11 (predicts cytotoxicity with certain RNR inhibitors)[2]RNR subunit expression (e.g., RRM1, RRM2 overexpression can confer resistance)

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