Mitochondrial deoxyguanosine kinase and cytoplasmic deoxycytidine kinase (DGUOK and dCK)

Mitochondrial deoxyguanosine kinase (DGUOK) and cytoplasmic deoxycytidine kinase (dCK) are key enzymes in the nucleoside salvage pathways responsible for the phosphorylation of deoxyribonucleosides and maintaining nucleotide pools for DNA replication and repair. DGUOK is targeted specifically to mitochondria, where it phosphorylates purine deoxyribonucleosides, contributing to the synthesis and maintenance of mitochondrial DNA. Mutations in DGUOK can cause severe inherited mitochondrial depletion syndromes, affecting liver, brain, and muscle function. dCK resides in the cytoplasm and phosphorylates deoxycytidine, deoxyadenosine, and deoxyguanosine, activating nucleoside analog drugs (like cytarabine, fludarabine, cladribine) used in cancer and viral disease treatment. Both enzymes are therapeutic targets for cancer and rare inherited diseases, and are associated with drug efficacy, biomarker utility, and safety challenges related to off-target toxicity and resistance mechanisms[1][3][4][5][6][7][8].

Other names

DGUOKmitochondrial deoxyguanosine kinasedCKdeoxyadenosine kinasedeoxyguanosine kinase (historically, but not recommended for dCK)

Phosphorylation of nucleoside analogs: Both DGUOK and dCK convert nucleoside analogs into their active monophosphate form, enabling their cytotoxic or antiviral activity. Disruption of DNA synthesis and repair: Activated analogs (by phosphorylation) are incorporated into DNA, causing cell death, particularly in cancer cells.