Highly potent dUTPase inhibition by a bacterial repressor protein reveals a novel mechanism for gene expression control

Judit E. Szabó, Veronika Németh, Veronika Papp-Kádár, Kinga Nyíri, Ibolya Leveles, Abris Bendes, Imre Zagyva, Gergely Róna, Hajnalka L. Pálinkás, Balázs Besztercei, Olivér Ozohanics, K. Vékey, K. Liliom, J. Tóth, B. Vértessy

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11912-11920
Number of pages9
JournalNucleic Acids Research
Volume42
Issue number19
DOIs
Publication statusPublished - Oct 29 2014

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Repressor Proteins
Bacterial Proteins
Gene Expression
Bacteriophages
Genomic Islands
Proteins
Genomic Instability
GTP-Binding Proteins
Virulence
Staphylococcus aureus
Nucleotides
dUTP pyrophosphatase
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Highly potent dUTPase inhibition by a bacterial repressor protein reveals a novel mechanism for gene expression control. / Szabó, Judit E.; Németh, Veronika; Papp-Kádár, Veronika; Nyíri, Kinga; Leveles, Ibolya; Bendes, Abris; Zagyva, Imre; Róna, Gergely; Pálinkás, Hajnalka L.; Besztercei, Balázs; Ozohanics, Olivér; Vékey, K.; Liliom, K.; Tóth, J.; Vértessy, B.

In: Nucleic Acids Research, Vol. 42, No. 19, 29.10.2014, p. 11912-11920.

Research output: Contribution to journalArticle

Szabó, JE, Németh, V, Papp-Kádár, V, Nyíri, K, Leveles, I, Bendes, A, Zagyva, I, Róna, G, Pálinkás, HL, Besztercei, B, Ozohanics, O, Vékey, K, Liliom, K, Tóth, J & Vértessy, B 2014, 'Highly potent dUTPase inhibition by a bacterial repressor protein reveals a novel mechanism for gene expression control', Nucleic Acids Research, vol. 42, no. 19, pp. 11912-11920. https://doi.org/10.1093/nar/gku882
Szabó, Judit E. ; Németh, Veronika ; Papp-Kádár, Veronika ; Nyíri, Kinga ; Leveles, Ibolya ; Bendes, Abris ; Zagyva, Imre ; Róna, Gergely ; Pálinkás, Hajnalka L. ; Besztercei, Balázs ; Ozohanics, Olivér ; Vékey, K. ; Liliom, K. ; Tóth, J. ; Vértessy, B. / Highly potent dUTPase inhibition by a bacterial repressor protein reveals a novel mechanism for gene expression control. In: Nucleic Acids Research. 2014 ; Vol. 42, No. 19. pp. 11912-11920.
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