Faculty Opinions recommendation of A bacterial toxin inhibits DNA replication elongation through a direct interaction with the β sliding clamp.

2014 ◽  
Author(s):  
Martin Marinus
Keyword(s):  
Dna Replication ◽  
Direct Interaction ◽  
Bacterial Toxin ◽  
Sliding Clamp

scholarly journals A Bacterial Toxin Inhibits DNA Replication Elongation through a Direct Interaction with the β Sliding Clamp

2013 ◽  
Vol 52 (5) ◽  
pp. 617-628 ◽  
Author(s):  
Christopher D. Aakre ◽  
Tuyen N. Phung ◽  
David Huang ◽  
Michael T. Laub
Keyword(s):  
Dna Replication ◽  
Direct Interaction ◽  
Bacterial Toxin ◽  
Sliding Clamp

scholarly journals Interaction of the Putative Human Cytomegalovirus Portal Protein pUL104 with the Large Terminase Subunit pUL56 and Its Inhibition by Benzimidazole-d-Ribonucleosides

2005 ◽  
Vol 79 (23) ◽  
pp. 14660-14667 ◽  
Author(s):  
Alexandra Dittmer ◽  
John C. Drach ◽  
Leroy B. Townsend ◽  
Anke Fischer ◽  
Elke Bogner
Keyword(s):  
Dna Replication ◽  
Human Cytomegalovirus ◽  
Unit Length ◽  
Large Subunit ◽  
Intracellular Localization ◽  
Direct Interaction ◽  
Portal Protein ◽  
Specific Association ◽  
Carboxy Terminal

ABSTRACT Herpesvirus DNA replication leads to unit length genomes that are translocated into preformed procapsids through a unique portal vertex. The translocation is performed by the terminase that cleaves the DNA and powers the insertion by its ATPase activity. Recently, we demonstrated that the putative human cytomegalovirus (HCMV) portal protein, pUL104, also forms high-molecular-weight complexes. Analyses now have been performed to determine the intracellular localization and identification of interaction partners of pUL104. In infected cells, HCMV pUL104 was found to be predominantly localized throughout the nucleus as well as in cytoplasmic clusters at late times of infection. The latter localization was abolished by phosphonoacetic acid, an inhibitor of viral DNA replication. Immunofluorescence revealed that pUL104 colocalized with pUL56, the large subunit of the HCMV terminase. Specific association of in vitro translated pUL104 with the carboxy-terminal half of GST-UL56C was detected. By using coimmunoprecipitations a direct interaction with pUL56 was confirmed. In addition, this interaction was no longer detected when the benzimidazole-d-nucleosides BDCRB or Cl4RB were added, thus indicating that these HCMV inhibitors block the insertion of the DNA into the capsid by preventing a necessary interaction of pUL56 with the portal. Electron microscopy revealed that in the presence of Cl4RB DNA is not packaged into capsids and these capsids failed to egress from the nucleus. Furthermore, pulsed-field gel electrophoresis showed that DNA concatemers synthesized in the presence of the compound failed to be processed.

scholarly journals Elements in the immunoglobulin heavy-chain enhancer directly regulate simian virus 40 ori-dependent DNA replication.

1993 ◽  
Vol 13 (9) ◽  
pp. 5629-5636 ◽  
Author(s):  
K Ariizumi ◽  
M R Ghosh ◽  
P W Tucker
Keyword(s):  
Dna Replication ◽  
Heavy Chain ◽  
Direct Interaction ◽  
Simian Virus 40 ◽  
Immunoglobulin Heavy Chain ◽  
Simian Virus ◽  
Regulatory Function ◽  
Chromosomal Dna ◽  
Chromosomal Replication ◽  
Sv40 Dna

In a previous study, we showed that the immunoglobulin heavy-chain (IgH) enhancer (IgHe) is near or in an initiation zone of chromosomal DNA replication, which is preferentially active in B cells (K. Ariizumi, Z. Wang, and P. W. Tucker, Proc. Natl. Acad. Sci. USA 90:3695-3699, 1993). This suggests the existence of a functional relationship between IgHe-mediated transcription and DNA replication. To test this theory, we utilized simian virus 40 (SV40) DNA replication as a model of chromosomal replication. IgHe or its operationally divisible domains (5'-En, core, and 3'-En) were introduced into SV40 minichromosomes (IgHe-SV40). Results of replication assays with IgHe-SV40 replicons indicated that the 5'-En and 3'-En activated or suppressed SV40 DNA replication regardless of the presence of SV40 enhancers or promoters in these replicons. The activity did not reside in IgHe core sequences. The results suggested that the 5'- and 3'-En regulated SV40 replication through direct interaction with the origin, not through suppression at the SV40 enhancer and/or promoter. In an effort to identify elements within the 5'-En motif that contributed to this effect, we found that the E site, but not microE5 and microE2 boxes, upregulated DNA replication. Our results provide another possible regulatory function for the 5'-En and 3'-En domains besides transcriptional suppression of IgHe.

scholarly journals Toxin–antitoxin operon kacAT of Klebsiella pneumoniae is regulated by conditional cooperativity via a W-shaped KacA–KacT complex

2019 ◽  
Vol 47 (14) ◽  
pp. 7690-7702 ◽  
Author(s):  
Hongliang Qian ◽  
Hao Yu ◽  
Peifei Li ◽  
E Zhu ◽  
Qingqing Yao ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Klebsiella Pneumoniae ◽  
Previous Analysis ◽  
Molecular Model ◽  
Direct Interaction ◽  
Bacterial Toxin ◽  
Multidrug Tolerance ◽  
Negative Autoregulation ◽  
Promoter Dna

AbstractBacterial toxin–antitoxin pairs play important roles in bacterial multidrug tolerance. Gcn5-related N-acetyltransferase (GNAT) toxins inhibit translation by acetylation of aminoacyl-tRNAs and are counteracted by direct contacts with cognate ribbon–helix–helix (RHH) antitoxins. Our previous analysis showed that the GNAT toxin KacT and RHH antitoxin KacA of Klebsiella pneumoniae form a heterohexamer in solution and that the complex interacts with the cognate promoter DNA, resulting in negative autoregulation of kacAT transcription. Here, we present the crystal structure of DNA-bound KacAT complex at 2.2 Å resolution. The crystal structure revealed the formation of a unique heterohexamer, KacT–KacA2–KacA2–KacT. The direct interaction of KacA and KacT involves a unique W-shaped structure with the two KacT molecules at opposite ends. Inhibition of KacT is achieved by the binding of four KacA proteins that preclude the formation of an active KacT dimer. The kacAT operon is auto-regulated and we present an experimentally supported molecular model proposing that the KacT:KacA ratio controls kacAT transcription by conditional cooperativity. These results yield a profound understanding of how transcription GNAT–RHH pairs are regulated.

Caulobacter crescentus β sliding clamp employs a noncanonical regulatory model of DNA replication

FEBS Journal ◽  
2019 ◽  
Vol 287 (11) ◽  
pp. 2292-2311 ◽  
Author(s):  
Xuguang Jiang ◽  
Linjuan Zhang ◽  
Jiancheng An ◽  
Mingxing Wang ◽  
Maikun Teng ◽  
...  
Keyword(s):  
Dna Replication ◽  
Caulobacter Crescentus ◽  
Sliding Clamp ◽  
Regulatory Model
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