dUTPase

Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is an enzyme that catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate. By rapidly converting dUTP to dUMP, it keeps the cellular dUTP pool low and maintains a favorable dUTP/dTTP ratio, thereby reducing incorporation of uracil into DNA during replication and repair. The generated dUMP feeds into thymidylate biosynthesis via thymidylate synthase, linking dUTPase activity to dTMP production and DNA synthesis.

Most dUTPases are homotrimers; each subunit contributes to a shared active site at the interface between subunits. They typically require divalent metal ions for catalysis and recognize the substrate dUTP with specificity; while the canonical trimeric form is widespread in bacteria, archaea and eukaryotes, some organisms and many viruses encode monomeric or structurally distinct variants.

Genes encoding dUTPase are named dut in bacteria and DUT in eukaryotes; in humans multiple isoforms exist, including nuclear/cytoplasmic and mitochondrial forms encoded by the same DUT gene or via alternative targeting sequences. In viruses, dUTPases are sometimes encoded to support genome replication, notably in herpesviruses and poxviruses.

Biological importance: dUTPase maintains genome stability by limiting uracil incorporation; deficiency or inhibition can lead to uracil misincorporation, activating DNA repair pathways and causing strand breaks. Because of its role in nucleotide metabolism, dUTPase is explored as a target for antiviral and anticancer therapies; inhibitors and plant/microbial dUTPases have been studied in various contexts.