DUTPase expression correlates with cell division potential in Drosophila melanogaster

Abstract

dUTP pyrophosphatase (dUTPase) is a dNTP-sanitizing enzyme that prevents the appearance of potentially harmful uracil bases in DNA by hydrolyzing cellular dUTP. This function of dUTPase is found to be essential in many organisms including Drosophila melanogaster. Previously, we showed that the expression pattern of dUTPase determines the extent of uracil accumulation in the genome of different tissues. We wished to find the regulatory mechanism that eventually leaves a set of tissues with a uracil-free and intact genome. We found that the expression pattern established by the promoter of Drosophila dUTPase overlaps with mRNA and protein expression, excluding the involvement of other post-transcriptional contributions. This promoter was found to be active in primordial tissues, such as in the imaginal discs of larvae, in the larval brain and in reproductive organs. In the case of brain and imaginal tissues, we observed that the promoter activity depends on a DNA replication-related element motif, the docking site of DNA replication-related element binding factor, which is known as a transcriptional activator of genes involved in replication and proliferation. These results suggest that dUTPase expression is fine-tuned to meet the requirements of DNA synthesis in tissues where the maintenance of genome integrity is of high importance.