Genomic DNA (DNA) (DNA)

Genomic DNA serves as the primary therapeutic target for the antimetabolite drug cytarabine, which is a cornerstone in the treatment of acute myeloid leukemia and other hematologic malignancies (StatPearls, 2023). Cytarabine, a pyrimidine nucleoside analog, functions as a prodrug that must be phosphorylated into its active form, cytarabine triphosphate (Ara-CTP), to exert its cytotoxic effects (PubChem, CID 6253). During the S-phase of the cell cycle, Ara-CTP is incorporated into the nascent DNA strand in place of the natural substrate, deoxycytidine triphosphate. This incorporation creates structural defects in the DNA backbone, effectively inhibiting the activity of DNA polymerases and halting further DNA chain elongation (Grant, 1998). The resulting interference with DNA replication and repair mechanisms activates apoptotic pathways, leading to the death of rapidly proliferating cancer cells. The clinical efficacy of targeting genomic DNA with cytarabine is often modulated by the expression of nucleoside transporters like hENT1 and activating enzymes such as deoxycytidine kinase (Galmarini et al., 2002). Consequently, genomic DNA remains a critical focal point for chemotherapy, though its non-specific nature leads to significant side effects like myelosuppression and neurotoxicity.

Other names

Nuclear DNAChromosomal DNADeoxyribonucleic acid

Cytarabine is intracellularly converted into cytarabine triphosphate (Ara-CTP), which competes with deoxycytidine triphosphate (dCTP) for incorporation into genomic DNA by DNA polymerases. Once incorporated, the arabinose sugar moiety causes steric hindrance that inhibits DNA polymerase alpha and beta, leading to DNA chain termination and the inhibition of DNA synthesis and repair. This process induces DNA strand breaks and triggers the DNA damage response, ultimately resulting in S-phase cell cycle arrest and programmed cell death (apoptosis).