Vertaisarvioitu alkuperäisartikkeli tai data-artikkeli tieteellisessä aikakauslehdessä (A1)
Highly potent dUTPase inhibition by a bacterial repressor protein reveals a novel mechanism for gene expression control
Julkaisun tekijät: Szabo JE, Nemeth V, Papp-Kadar V, Nyiri K, Leveles I, Bendes AA, Zagyva I, Rona G, Palinkas HL, Besztercei B, Ozohanics O, Vekey K, Liliom K, Toth J, Vertessy BG
Kustantaja: OXFORD UNIV PRESS
Julkaisuvuosi: 2014
Journal: Nucleic Acids Research
Tietokannassa oleva lehden nimi: NUCLEIC ACIDS RESEARCH
Lehden akronyymi: NUCLEIC ACIDS RES
Volyymi: 42
Aloitussivu: 11912
Lopetussivun numero: 11920
Sivujen määrä: 9
ISSN: 0305-1048
DOI: http://dx.doi.org/10.1093/nar/gku882
Tiivistelmä
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 Phi 11 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.
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 Phi 11 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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