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

Hirmondó, R. and Szabó, JE. and Nyíri, K. and Tarjányi, S. and Dobrotka, P. and Vértessy (Grolmuszné), Beáta (2015) Cross-species inhibition of dUTPase via the Staphylococcal Stl protein perturbs dNTP pool and colony formation in Mycobacterium. MUTATION RESEARCH-DNA REPAIR, 30. pp. 21-27. ISSN 1568-7864

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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.

Item Type: Article
Uncontrolled Keywords: Staphylococcus aureus; Staphylococcus; Mycobacterium tuberculosis; Mycobacterium smegmatis; Mycobacterium; Corynebacterineae; Staphylococcal repressor; High cellular dUTP level; Genome integrity; DUTPase inhibitor protein
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 16 May 2015 06:04
Last Modified: 16 May 2015 06:04
URI: http://real.mtak.hu/id/eprint/24108

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