DNA polymerase and Ribonucleotide reductase (DNA Pol / RNR)

DNA polymerase and ribonucleotide reductase (RNR) are essential components of the cellular machinery required for DNA replication and repair. Ribonucleotide reductase is the rate-limiting enzyme that converts ribonucleotides into deoxyribonucleotides (dNTPs), which serve as the fundamental building blocks for DNA (StatPearls, 2023). DNA polymerases subsequently catalyze the polymerization of these dNTPs into a DNA strand, ensuring accurate transmission of genetic information (UniProt, 2024). This enzymatic axis is a primary target for antimetabolite drugs, particularly nucleoside analogs used in oncology. These drugs, such as gemcitabine and fludarabine, act as antimetabolites that inhibit RNR to deplete dNTP pools and are incorporated into DNA by polymerases to cause chain termination and genomic instability (PubMed: PMC3760780). The resulting inhibition of DNA synthesis triggers cell cycle arrest and apoptosis, making these enzymes critical targets for treating various hematological malignancies and solid tumors.

Other names

DNA synthesis machineryRNR/DNA Pol axisNucleoside analog targetsDNA polymerase and DNA

Dual inhibition involving the depletion of deoxyribonucleotide pools via ribonucleotide reductase inhibition and the subsequent inhibition of DNA synthesis through DNA polymerase competition and chain termination (PubMed: PMC3760780).