2'-Deoxynucleoside 5'-phosphate N-hydrolase 1 (DNPH1)

2'-Deoxynucleoside 5'-phosphate N-hydrolase 1 (DNPH1) is an enzyme that catalyzes the hydrolysis of the N-glycosidic bond of 5-hydroxymethyl-2'-deoxyuridine 5'-monophosphate (5hmdUMP), producing 2-deoxyribose 5-phosphate and 5-hydroxymethyluracil[1][4]. This reaction is a critical step in a nucleotide salvage pathway that eliminates cytotoxic epigenetically modified nucleotides and prevents their aberrant incorporation into DNA. DNPH1 activity is c-Myc responsive and may be involved in cellular proliferation, differentiation, and apoptosis pathways[3]. Overexpression of DNPH1 in cancer cells leads to resistance to poly(ADP-ribose) polymerase inhibitors (PARPi), and inhibition of DNPH1 can enhance sensitivity to these anticancer agents, making DNPH1 an attractive therapeutic target in oncology[1][5]. Its molecular family is distinct from nucleoside 2'-deoxyribosyltransferases, sharing structural and mechanistic features that rely on a catalytic glutamate residue in covalent catalysis[1].

Other names

5-hydroxymethyl-dUMP N-hydrolaseC6orf108RCLrcldJ330M21.3c-Myc-responsive protein RCLdeoxyribonucleoside 5'-monophosphate N-glycosidase

DNPH1 inhibition leads to increased accumulation of 5-hydroxymethyl-dUMP in DNA, promoting PARP trapping in cancer cells and resensitizing them to PARP inhibitors[1][5]