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Nucleic Acids Res. 2014 Oct 29;42(19):11912-20. doi: 10.1093/nar/gku882. Epub 2014 Oct 1.

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

Author information

1
Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary vertessy@mail.bme.hu vertessy.beata@ttk.mta.hu.
2
Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary.
3
Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary.
4
Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary Doctoral School of Multidisciplinary Medical Science, University of Szeged, Szeged, Hungary.
5
Institutes of Enzymology and Organic Chemistry, RCNS, Hungarian Academy of Sciences, Budapest, Hungary Department of Applied Biotechnology and Food Sciences, Budapest University of Technology and Economics, Budapest, Hungary vertessy@mail.bme.hu vertessy.beata@ttk.mta.hu.

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.

PMID:
25274731
PMCID:
PMC4231751
DOI:
10.1093/nar/gku882
[Indexed for MEDLINE]
Free PMC Article

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