Incorporation into DNA via nucleotide metabolism pathways

Incorporation into DNA via nucleotide metabolism pathways is a complex pharmacological process rather than a single molecular target. It involves the uptake and subsequent metabolic activation of nucleoside or nucleotide analogs, which are chemically modified versions of natural DNA building blocks. These analogs are phosphorylated by cellular kinases into active triphosphate forms that compete with endogenous deoxyribonucleotide triphosphates (dNTPs) for incorporation into nascent DNA strands by DNA polymerases (StatPearls, 2023). Once integrated, these fraudulent nucleotides often cause premature chain termination or create structural distortions that impede further replication and transcription (PubMed, PMID: 15591235). This mechanism is a hallmark of many antimetabolite drugs used in oncology and virology, effectively inducing cell cycle arrest and apoptosis in rapidly dividing cells (NCI, 2024). However, because this process affects fundamental DNA synthesis, it is associated with significant systemic toxicities, particularly in the hematopoietic and gastrointestinal systems (PubMed, PMID: 12748669).

Other names

DNA incorporation of antimetabolitesNucleoside analog incorporationFraudulent nucleotide incorporationAntimetabolite-mediated DNA damage

Nucleoside analogs are phosphorylated by cellular kinases to their active triphosphate forms, which compete with natural dNTPs for incorporation into DNA by DNA polymerases, leading to chain termination or DNA damage (StatPearls, 2023; PubMed, PMID: 15591235).