Disease relevance of Dut

• In this report, HSV-1 strain 17 syn+ and two isogenic engineered dUTPase-negative mutants were characterized in the mouse model [1].

High impact information on Dut

• Following intracranial inoculation, a recombinant expressing VP5 from a strict-late promoter (U(L)38) exhibited an increased 50% lethal dose and a 10-fold decrease in virus yields in the central nervous system, while a recombinant expressing VP5 from an early (dUTPase) or another leaky-late (VP16) promoter exhibited wild-type neurovirulence [2].
• To assess whether uracil DNA glycosylase and dUTP nucleotidohydrolase (dUTPase) can be involved in repair-type DNA synthesis associated to crossing-over or induced by UV and X-ray treatments, we have studied these enzyme activities in male mouse germ cells at specific stages of differentiation [3].
• Unlike rat dUTPase, mouse dUTPase failed to bind PPARalpha [4].
• In situ hybridization and immunohistochemical studies revealed that, in the adult mouse, dUTPase is expressed at high levels in proliferating cells of colonic mucosa, and of germinal epithelium in testis [4].
• We now report the cloning of mouse dUTPase cDNA and show that it contains a 162-amino acid open reading frame, encoding a protein with a predicted Mr of 17,400 and differs from rat cDNA, which contains additional 43 amino acids at the N-terminal end [4].

Biological context of Dut

• These observations suggest the existence of variants of dUTPase, some of which may influence nuclear receptor function during development and differentiation, in addition to catalyzing the hydrolysis of dUTP to dUMP [4].
• At 9.5-day mouse embryonic development, dUTPase expression is predominantly in developing neural epithelium, and hepatic primordium, and in later developmental stages (11.5-, 13.5-, and 15.5-day embryo), the expression began to be localized to the liver, kidney, gut epithelium, thymus, granular layer of the cerebellum, and olfactory epithelium [4].
• The data reported suggest that, in this biological system, the main role of dUTPase is to degrade dUTP to prevent misincorporation of uracil into DNA during crossing-over, rather than to participate in the biosynthetic pathway of dTTP [3].

Associations of Dut with chemical compounds

• We have previously reported the cloning of rat deoxyuridine triphosphate nucleotidohydrolase (dUTPase) cDNA and demonstrated that the full-length protein as well as the N-terminal 62-amino acid peptide interacts with peroxisome proliferator-activated receptor alpha (PPARalpha) [4].

References