Ribonucleoside-diphosphate reductase and DNA (RNR and DNA)

Ribonucleoside-diphosphate reductase (RNR) is an essential enzyme complex that catalyzes the rate-limiting step in the de novo synthesis of deoxyribonucleotides (dNTPs), which are the fundamental building blocks for DNA replication and repair (StatPearls, 2023). The enzyme reduces ribonucleoside diphosphates into their corresponding deoxyribonucleoside forms, maintaining the balanced nucleotide pools necessary for genomic stability (UniProt, 2024). Because rapidly proliferating cancer cells require a constant supply of dNTPs to support DNA synthesis, RNR is a critical target for oncological therapies (NCBI, 2021). Drugs such as hydroxyurea inhibit RNR by quenching the tyrosyl radical in the RRM2 subunit, while antimetabolites like gemcitabine act as suicide inhibitors of the enzyme and are subsequently incorporated into the DNA structure itself (PubMed, 2018). This dual mechanism of depleting DNA precursors and directly damaging the DNA template effectively halts the cell cycle and triggers programmed cell death in malignant tissues.

Other names

Ribonucleotide reductaseRNRDeoxyribonucleic acidRibonucleoside-diphosphate reductase complexDNA

Inhibition of the ribonucleoside-diphosphate reductase (RNR) enzyme prevents the conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, thereby depleting the dNTP pools required for DNA replication and repair. Additionally, many drugs targeting this pathway are nucleoside analogs that, after inhibiting RNR, are phosphorylated and incorporated into DNA, leading to DNA strand termination and the inhibition of DNA polymerases (StatPearls, 2023; PubMed, 2018).