dNDPs

Deoxynucleotide diphosphates (dNDPs) are deoxyribonucleoside diphosphates, molecules consisting of a deoxyribonucleoside linked to two phosphate groups. They function as intermediates in the intracellular metabolism of deoxynucleotides and in the maintenance of the dNTP pool required for DNA replication and repair. The four base-specific dNDPs are dADP, dCDP, dGDP, and dTDP.

Formation and interconversion occur through phosphorylation and dephosphorylation reactions that connect the monophosphate, diphosphate, and triphosphate forms. Deoxynucleoside monophosphates (dNMPs) are phosphorylated to dNDPs by specific deoxynucleoside kinases, and dNDPs are further phosphorylated to dNTPs by nucleotide kinases, including nucleoside diphosphate kinases (NDKs) that mediate interconversion between NDPs and NTPs. Conversely, hydrolases and phosphatases can remove phosphate groups, returning dNDPs to dNMPs. This network helps regulate the balance between different phosphorylation states and base-specific pools.

Biological significance centers on the tight control of the dNTP pool. Adequate and balanced dNTP levels are essential for high-fidelity DNA synthesis and repair; imbalances or accumulation of particular dNDPs or dNTPs can increase replication stress and mutagenesis, or cause cytotoxic effects. dNDPs are present across organisms and participate in both de novo and salvage pathways of nucleotide metabolism, contributing to overall nucleotide homeostasis in the cell. They are also relevant in research and clinical contexts for studying DNA synthesis and nucleotide metabolism.