DNA polymerase and ribonucleotide reductase (DNA synthesis machinery) (RNR/DNA Pol)

The DNA synthesis machinery, specifically the functional coupling of ribonucleotide reductase (RNR) and DNA polymerase, is the cornerstone of cellular replication and genome maintenance. Ribonucleotide reductase serves as the rate-limiting enzyme that converts ribonucleoside diphosphates into deoxyribonucleoside diphosphates, ensuring a sufficient and balanced supply of dNTPs for DNA synthesis (StatPearls, 2023). DNA polymerases then utilize these dNTPs to assemble new DNA strands during the S-phase of the cell cycle or during DNA repair (Nature Education, 2014). Because rapidly proliferating cancer cells and replicating viruses are highly dependent on this machinery, it has become a primary focus for therapeutic intervention. Antimetabolite drugs like gemcitabine and clofarabine exert their effects by inhibiting RNR to deplete dNTP pools while simultaneously acting as substrate analogs that DNA polymerase incorporates into nascent strands, leading to chain termination (NCBI, 2021). This dual-action mechanism effectively halts replication forks and triggers programmed cell death in target cells. Additionally, selective inhibition of viral DNA polymerases by agents such as acyclovir remains a standard approach for treating herpesvirus infections (PubMed, 2019).

Other names

DNA replication machinerydNTP synthesis and polymerization complexDNA replicase complexDNA replication fork machinery

Inhibition of deoxyribonucleotide production via RNR and competitive inhibition of DNA strand elongation via DNA polymerase.