Cytidine and dCMP deaminase domain-containing protein 1 (CDADC1)

Cytidine and dCMP deaminase domain-containing protein 1 (CDADC1) is a vertebrate-specific enzyme containing two cytidine deaminase domains, only one of which is catalytically active. Its main function is to catalyze the deamination of deoxycytidine triphosphate (dCTP) to deoxyuridine triphosphate (dUTP). Unlike classical cytidine or dCMP deaminases, CDADC1 does not act on dCMP, cytidine, or deoxycytidine, but is specific for (deoxy-)CTP in its triphosphate form. It plays a role in nucleotide metabolism and influences cellular response to chemotherapeutic agents gemcitabine and decitabine by directly metabolizing their active triphosphate forms. CDADC1 is highly expressed in the testis and developmentally regulated, suggesting an additional role in testicular development and spermatogenesis. Disruption of CDADC1 does not significantly impair viability or fertility in mice but renders them hypersensitive to certain nucleoside analog chemotherapeutics, thus presenting both as a metabolic modulator of cancer drug response and a safety-related biomarker during treatment.[1][2][3][4]

Other names

NYD-SP15testis development protein NYD-SP15protein kinase NYD-SP15bA103J18.1cytidine deaminase (incorrect, see below)

Deamination of the active triphosphate forms of gemcitabine and decitabine, which leads to their metabolic inactivation by conversion to their uracil analog triphosphates; these are then further hydrolyzed and prevented from being incorporated into DNA[1][4]