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

The DNA synthesis machinery, specifically the enzymes DNA polymerase and ribonucleotide reductase (RNR), is essential for cellular replication and genome integrity (Nordlund & Reichard, 2006). Ribonucleotide reductase serves as the rate-limiting step in DNA synthesis by converting ribonucleoside diphosphates into deoxyribonucleoside diphosphates, thereby maintaining the necessary pools of dNTPs (Singh & Xu, 2016). DNA polymerases then utilize these dNTPs to synthesize new DNA strands during the S-phase of the cell cycle or during DNA repair processes (Hubscher et al., 2002). Because cancer cells exhibit accelerated proliferation and a heightened requirement for DNA precursors, this machinery is a major target for chemotherapy. Antimetabolites such as gemcitabine and hydroxyurea inhibit RNR, while nucleoside analogs like cytarabine and fludarabine act as competitive inhibitors or chain terminators of DNA polymerase (Cerqueira et al., 2007). Therapeutic targeting of these enzymes effectively induces replication stress and apoptosis in malignant cells, though it frequently results in off-target effects on healthy, rapidly dividing tissues such as bone marrow.

Other names

DNA replication complexReplisome componentsRibonucleoside-diphosphate reductaseDNA-directed DNA polymerase

Inhibition of deoxyribonucleotide synthesis via ribonucleotide reductase and competitive inhibition or chain termination of DNA synthesis via DNA polymerase.