DNA synthesis machinery via nucleoside metabolism

DNA synthesis machinery via nucleoside metabolism refers to the integrated network of enzymes and transporters responsible for the production of deoxyribonucleotide triphosphates (dNTPs) and their subsequent assembly into DNA strands (Source [3], [7]). This system includes the de novo and salvage pathways of nucleoside metabolism, featuring key enzymes such as ribonucleotide reductase (RNR), thymidylate synthase (TS), and dihydrofolate reductase (DHFR), as well as the DNA polymerases that execute replication (Source [7], [8]). Because rapidly dividing cells, such as cancer cells and virally infected cells, have an increased demand for DNA precursors, this machinery is a critical therapeutic target (Source [1], [5]). Nucleoside transporters, such as the SLC28 and SLC29 families, are also essential components that mediate the cellular uptake of these therapeutic agents (Source [10]). Antimetabolite drugs, including gemcitabine, 5-fluorouracil, and methotrexate, exert their effects by inhibiting these metabolic enzymes or by acting as fraudulent nucleoside analogs that incorporate into DNA, leading to chain termination or lethal mutations (Source [3], [7]). While highly effective in slowing disease progression, these agents often cause systemic toxicity, particularly in the bone marrow and gastrointestinal tract, due to their impact on normal proliferating cells (Source [3], [4]). Biomarkers such as PCNA and Ki-67 are frequently used to assess the activity of this machinery in clinical settings (Source [1], [2]).

Other names

DNA replication machineryNucleotide biosynthesis pathwayNucleoside metabolic pathwayDNA synthesis pathway

Inhibition of nucleotide biosynthesis enzymes (e.g., ribonucleotide reductase, thymidylate synthase, dihydrofolate reductase), competitive inhibition of DNA polymerases, and incorporation into DNA leading to chain termination or masked chain termination.