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Highly potent dUTPase inhibition by a bacterial repressor protein reveals a novel mechanism for gene expression control |
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| Authors: | Judit E Szabó Veronika Németh Veronika Papp-Kádár Kinga Nyíri Ibolya Leveles ábris á Bendes Imre Zagyva Gergely Róna Hajnalka L Pálinkás Balázs Besztercei Olivér Ozohanics Károly Vékey Károly Liliom Judit Tóth Beáta G Vértessy |
| Institution: | 1.Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary;2.Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary;3.Doctoral School of Multidisciplinary Medical Science, University of Szeged, Szeged, Hungary |
| Abstract: | Transfer of phage-related pathogenicity islands of Staphylococcus aureus (SaPI-s) was recently reported to be activated by helper phage dUTPases. This is a novel function for dUTPases otherwise involved in preservation of genomic integrity by sanitizing the dNTP pool. Here we investigated the molecular mechanism of the dUTPase-induced gene expression control using direct techniques. The expression of SaPI transfer initiating proteins is repressed by proteins called Stl. We found that Φ11 helper phage dUTPase eliminates SaPIbov1 Stl binding to its cognate DNA by binding tightly to Stl protein. We also show that dUTPase enzymatic activity is strongly inhibited in the dUTPase:Stl complex and that the dUTPase:dUTP complex is inaccessible to the Stl repressor. Our results disprove the previously proposed G-protein-like mechanism of SaPI transfer activation. We propose that the transfer only occurs if dUTP is cleared from the nucleotide pool, a condition promoting genomic stability of the virulence elements. |
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