ArticleScientific reports2017
Differential control of dNTP biosynthesis and genome integrity maintenance by the dUTPase superfamily enzymes.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- A randomized, observer-blind, phase 1 study of immune responses to three human adenovirus type 26 vector-based vaccines.EBioMedicine · 2026Trial
- A c-di-AMP-controlled glutamine synthesis pathway promotes persistence ofbioRxiv : the preprint server for biology · 2026Article
- dUTPase modulates mycobacterial homologous recombination and interacts with the AdnAB helicase-nuclease.Nucleic acids research · 2026Article
- dUTPase is essential in zebrafish development and possesses several single-nucleotide variants with pronounced structural and functional consequences.FEBS open bio · 2026Article
- Full-length inhibitor protein is the most effective to perturb human dUTPase activity.Scientific reports · 2025Article
- Genetic stability ofeLife · 2024Article
- The homodimerization domain of the Stl repressor is crucial for efficient inhibition of mycobacterial dUTPase.Scientific reports · 2024Article
- Using Selective Enzymes to Measure Noncanonical DNA Building Blocks: dUTP, 5-Methyl-dCTP, and 5-Hydroxymethyl-dCTP.Biomolecules · 2023Article
- Discovery of two new isoforms of the human DUT gene.Scientific reports · 2023Article
- Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability.Scientific reports · 2021Article
- Malic enzyme 2 connects the Krebs cycle intermediate fumarate to mitochondrial biogenesis.Cell metabolism · 2021Article
- Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD.Molecular cell · 2021Article
- Deoxyuracil in DNA in health and disease.Current opinion in clinical nutrition and metabolic care · 2020Review
- A user-friendly, high-throughput tool for the precise fluorescent quantification of deoxyribonucleoside triphosphates from biological samples.Nucleic acids research · 2020Article
- Targeting Genome Integrity inMolecules (Basel, Switzerland) · 2020Review
- Beyond Chelation: EDTA Tightly Binds Taq DNA Polymerase, MutT and dUTPase and Directly Inhibits dNTPase Activity.Biomolecules · 2019Article
- Article
- The Role of a Key Amino Acid Position in Species-Specific Proteinaceous dUTPase Inhibition.Biomolecules · 2019Article
- CRISPR/Cas9-Mediated Knock-Out of dUTPase in Mice Leads to Early Embryonic Lethality.Biomolecules · 2019Article
- Enzyme kinetics of dUTPase from the planarian Dugesia ryukyuensis.BMC research notes · 2019Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
dUTPase superfamily enzymes generate dUMP, the obligate precursor for de novo dTTP biosynthesis, from either dUTP (monofunctional dUTPase, Dut) or dCTP (bifunctional dCTP deaminase/dUTPase, Dcd:dut). In addition, the elimination of dUTP by these enzymes prevents harmful uracil incorporation into DNA. These two beneficial outcomes have been thought to be related. Here we determined the relationship between dTTP biosynthesis (dTTP/dCTP balance) and the prevention of DNA uracilation in a mycobacterial model that encodes both the Dut and Dcd:dut enzymes, and has no other ways to produce dUMP. We show that, in dut mutant mycobacteria, the dTTP/dCTP balance remained unchanged, but the uracil content of DNA increased in parallel with the in vitro activity-loss of Dut accompanied with a considerable increase in the mutation rate. Conversely, dcd:dut inactivation resulted in perturbed dTTP/dCTP balance and two-fold increased mutation rate, but did not increase the uracil content of DNA. Thus, unexpectedly, the regulation of dNTP balance and the prevention of DNA uracilation are decoupled and separately brought about by the Dcd:dut and Dut enzymes, respectively. Available evidence suggests that the discovered functional separation is conserved in humans and other organisms.
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