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A phage-encoded inhibitor of Escherichia coli DNA replication targets the DNA polymerase clamp loader.
Mol Microbiol. 2011 Mar; 79(5):1325-38
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20 May 2011
Martin Marinus
F1000 Microbiology
University of Massachusetts Medical School,
Worcester, Massachusetts, USA.
F1000 Microbiology
University of Massachusetts Medical School,
Worcester, Massachusetts, USA.
New Finding
DOI: 10.3410/f.10652956.11531054
Host DNA replication needs to be shut down during lytic bacteriophage infection and this study shows that phage N4 does so by directly inhibiting the host replicative DNA polymerase.
The authors showed that the phage-encoded gp8 protein targets the clamp loader assembly of host DNA polymerase III holoenzyme....Continue reading
The authors showed that the phage-encoded gp8 protein targets the clamp loader assembly of host DNA polymerase III holoenzyme....Continue reading
Host DNA replication needs to be shut down during lytic bacteriophage infection and this study shows that phage N4 does so by directly inhibiting the host replicative DNA polymerase.
The authors showed that the phage-encoded gp8 protein targets the clamp loader assembly of host DNA polymerase III holoenzyme. Specifically, it interacts with the HolA (delta) subunit to prevent the loading of the beta clamp (PCNA in eukaryotes), which is required for lagging DNA strand synthesis and for processivity.
The authors speculate that gp8 action allows for the conservation of host dNTP pools, which can then be used for phage DNA replication.
The authors showed that the phage-encoded gp8 protein targets the clamp loader assembly of host DNA polymerase III holoenzyme. Specifically, it interacts with the HolA (delta) subunit to prevent the loading of the beta clamp (PCNA in eukaryotes), which is required for lagging DNA strand synthesis and for processivity.
The authors speculate that gp8 action allows for the conservation of host dNTP pools, which can then be used for phage DNA replication.
Disclosures
None declared
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Marinus M: F1000Prime Recommendation of [Yano ST and Rothman-Denes LB, Mol Microbiol 2011, 79(5):1325-38]. In F1000Prime, 20 May 2011; DOI: 10.3410/f.10652956.11531054. F1000Prime.com/10652956#eval11531054
F1000Prime Recommendations, Dissents and Comments for [Yano ST and Rothman-Denes LB, Mol Microbiol 2011, 79(5):1325-38]. In F1000Prime, 21 May 2013; F1000Prime.com/10652956
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Coliphage N4 infection leads to shut-off of host DNA replication without inhibition of host transcription or translation. We report the identification and characterization of gp8, the N4 gene product responsible for this phenotype. N4 gp8 is an Escherichia coli bacteriostatic inhibitor that colocalizes with the E. coli replisome in a replication-dependent manner. Gp8 was purified and observed to cross-link to complexes containing the replicative DNA polymerase, DNAP III, in vivo. Purified gp8 inhibits DNA polymerization by DNA polymerase III holoenzyme in vitro by interfering with polymerase processivity. Gp8 specifically inhibits the clamp-loading activity of DNAP III by targeting the delta subunit of the DNAP III clamp loader; E. coli mutations conferring gp8 resistance were identified in the holA gene, encoding delta. Delta and gp8 interact in vitro; no interaction was detected between gp8 inactive mutants and wild-type delta or between delta gp8-resistant mutants and wild-type gp8. Therefore, this work identifies the DNAP III clamp loader as a new target for inhibition of bacterial growth. Finally, we show that gp8 is not essential in N4 development under laboratory conditions, but its activity contributes to phage yield.
© 2011 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2010.07526.x
PMID: 21205014
