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• W2734622020 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." @default.
• W2734622020 created "2017-07-21" @default.
• W2734622020 creator A5004002637 @default.
• W2734622020 creator A5008774671 @default.
• W2734622020 creator A5073086096 @default.
• W2734622020 creator A5079965006 @default.
• W2734622020 creator A5083525912 @default.
• W2734622020 date "2017-07-20" @default.
• W2734622020 modified "2023-10-10" @default.
• W2734622020 title "Differential control of dNTP biosynthesis and genome integrity maintenance by the dUTPase superfamily enzymes" @default.
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• W2734622020 doi "https://doi.org/10.1038/s41598-017-06206-y" @default.
• W2734622020 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5519681" @default.
• W2734622020 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28729658" @default.
• W2734622020 hasPublicationYear "2017" @default.
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