Cross-species inhibition of dUTPase via the Staphylococcal Stl protein perturbs dNTP pool and colony formation in Mycobacterium

Rita Hirmondó, Judit E. Szabó, Kinga Nyíri, Szilvia Tarjányi, Paula Dobrotka, Judit Tóth, Beáta G. Vértessy

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Proteins responsible for the integrity of the genome are often used targets in drug therapies against various diseases. The inhibitors of these proteins are also important to study the pathways in genome integrity maintenance. A prominent example is Ugi, a well known cross-species inhibitor protein of the enzyme uracil-DNA glycosylase, responsible for uracil excision from DNA. Here, we report that a Staphylococcus pathogenicity island repressor protein called StlSaPIbov1 (Stl) exhibits potent dUTPase inhibition in Mycobacteria. To our knowledge, this is the first indication of a cross-species inhibitor protein for any dUTPase. We demonstrate that the Staphylococcus aureus Stl and the Mycobacterium tuberculosis dUTPase form a stable complex and that in this complex, the enzymatic activity of dUTPase is strongly inhibited. We also found that the expression of the Stl protein in Mycobacterium smegmatis led to highly increased cellular dUTP levels in the mycobacterial cell, this effect being in agreement with its dUTPase inhibitory role. In addition, Stl expression in M. smegmatis drastically decreased colony forming ability, as well, indicating significant perturbation of the phenotype. Therefore, we propose that Stl can be considered to be a cross-species dUTPase inhibitor and may be used as an important reagent in dUTPase inhibition experiments either in vitro/in situ or in vivo.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalDNA Repair
Volume30
DOIs
Publication statusPublished - Jun 1 2015

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Keywords

  • DUTPase inhibitor protein
  • Genome integrity
  • High cellular dUTP level
  • Staphylococcal repressor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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