Competition of bacteriophage polypeptides with native replicase proteins for binding to the DNA sliding clamp reveals a novel mechanism for DNA replication arrest in Staphylococcus aureus. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecular Microbiology Année : 2006

Competition of bacteriophage polypeptides with native replicase proteins for binding to the DNA sliding clamp reveals a novel mechanism for DNA replication arrest in Staphylococcus aureus.

Adam Belley
  • Fonction : Auteur
Mario Callejo
  • Fonction : Auteur
Francis Arhin
  • Fonction : Auteur
Mohammed Dehbi
  • Fonction : Auteur
Ibtihal Fadhil
  • Fonction : Auteur
Jing Liu
Geoffrey Mckay
  • Fonction : Auteur
Ramakrishnan Srikumar
  • Fonction : Auteur
Pascale Bauda
Dominique Bergeron
  • Fonction : Auteur
Nhuan Ha
  • Fonction : Auteur
Philippe Gros
Jerry Pelletier
  • Fonction : Auteur
Greg Moeck
  • Fonction : Auteur

Résumé

Bacteriophages have evolved specific mechanisms that redirect bacterial metabolic pathways to the bacteriophage reproduction cycle. In this study, we characterized the bactericidal mechanism of two polypeptides from bacteriophages Twort and G1 that target the DNA sliding clamp of Staphylococcus aureus. The DNA sliding clamp, which tethers DNA polymerase to its template and thereby confers processivity upon the enzyme, was found to be essential for the viability of S. aureus. Expression of polypeptides TwortORF168 and G1ORF240 in S. aureus selectively inhibited DNA replication which in turn resulted in cell death. Both polypeptides specifically inhibited the S. aureus DNA replicase that was reconstituted in vitro but not the corresponding replicase of Streptococcus pyogenes. We demonstrated that inhibition of DNA synthesis is multifaceted and occurs via binding the DNA sliding clamp: TwortORF168 and G1ORF240 bound tightly to the DNA sliding clamp and prevented both its loading onto DNA and its interaction with DNA polymerase C. These results elucidate the impact of bacteriophage polypeptide expression upon DNA replication in the growing cell.

Dates et versions

hal-00194898 , version 1 (07-12-2007)

Identifiants

Citer

Adam Belley, Mario Callejo, Francis Arhin, Mohammed Dehbi, Ibtihal Fadhil, et al.. Competition of bacteriophage polypeptides with native replicase proteins for binding to the DNA sliding clamp reveals a novel mechanism for DNA replication arrest in Staphylococcus aureus.. Molecular Microbiology, 2006, 62 (4), pp.1132-43. ⟨10.1111/j.1365-2958.2006.05427.x⟩. ⟨hal-00194898⟩
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