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The metabolic control of DNA replication: mechanism and function (2023)
Journal Article
Soultanas, P., & Janniere, L. (2023). The metabolic control of DNA replication: mechanism and function. Open Biology, 13(8), Article 230220. https://doi.org/10.1098/rsob.230220

Metabolism and DNA replication are the two most fundamental biological functions in life. The catabolic branch of metabolism breaks down nutrients to produce energy and precursors used by the anabolic branch of metabolism to synthesize macromolecules... Read More about The metabolic control of DNA replication: mechanism and function.

The DNA replication initiation protein DnaD recognises a specific strand of the Bacillus subtilis chromosome origin (2023)
Journal Article
Winterhalter, C., Pelliciari, S., Stevens, D., Fenyk, S., Marchand, E., Cronin, N., …Murray, H. (2023). The DNA replication initiation protein DnaD recognises a specific strand of the Bacillus subtilis chromosome origin. Nucleic Acids Research, 51(9), 4322-4340. https://doi.org/10.1093/nar/gkad277

Genome replication is a fundamental biological activity shared by all organisms. Chromosomal replication proceeds bidirectionally from origins, requiring the loading of two helicases, one for each replisome. However, the molecular mechanisms underpin... Read More about The DNA replication initiation protein DnaD recognises a specific strand of the Bacillus subtilis chromosome origin.

The Replicative DnaE Polymerase of Bacillus subtilis Recruits the Glycolytic Pyruvate Kinase (PykA) When Bound to Primed DNA Templates (2023)
Journal Article
Holland, A., Pitoulias, M., Soultanas, P., & Janniere, L. (2023). The Replicative DnaE Polymerase of Bacillus subtilis Recruits the Glycolytic Pyruvate Kinase (PykA) When Bound to Primed DNA Templates. Life, 13(4), Article 965. https://doi.org/10.3390/life13040965

The glycolytic enzyme PykA has been reported to drive the metabolic control of replication through a mechanism involving PykA moonlighting functions on the essential DnaE polymerase, the DnaC helicase and regulatory determinants of PykA catalytic act... Read More about The Replicative DnaE Polymerase of Bacillus subtilis Recruits the Glycolytic Pyruvate Kinase (PykA) When Bound to Primed DNA Templates.

Ferric Quinate (QPLEX) inhibits the interaction of Major Outer Membrane Protein (MOMP) with the Lewis b (Leb) antigen and Limits Campylobacter colonisation in broilers (2023)
Journal Article
Okoye, J. C., Holland, A., Pitoulias, M., Paschalis, V., Piddubnyi, A., Dufailu, O. A., …Soultanos, P. (2023). Ferric Quinate (QPLEX) inhibits the interaction of Major Outer Membrane Protein (MOMP) with the Lewis b (Leb) antigen and Limits Campylobacter colonisation in broilers. Frontiers in Microbiology, 14, Article 1146418. https://doi.org/10.3389/fmicb.2023.1146418

Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major... Read More about Ferric Quinate (QPLEX) inhibits the interaction of Major Outer Membrane Protein (MOMP) with the Lewis b (Leb) antigen and Limits Campylobacter colonisation in broilers.

Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers (2023)
Journal Article
Okoye, J. C., Holland, A., Pitoulias, M., Paschalis, V., Piddubnyi, A., Dufailu, O. A., …Soultanas, P. (2023). Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers. Frontiers in Microbiology, 14, Article 1146418. https://doi.org/10.3389/fmicb.2023.1146418

Campylobacter jejuni colonizes hosts by interacting with Blood Group Antigens (BgAgs) on the surface of gastrointestinal epithelia. Genetic variations in BgAg expression affects host susceptibility to C. jejuni. Here, we show that the essential major... Read More about Ferric quinate (QPLEX) inhibits the interaction of major outer membrane protein (MOMP) with the Lewis b (Leb) antigen and limits Campylobacter colonization in broilers.

Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing (2023)
Journal Article
He, L., Lever, R., Cubbon, A., Tehseen, M., Jenkins, T., Nottingham, A. O., …Bolt, E. L. (2023). Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing. Nucleic Acids Research, 51(4), 1740-1749. https://doi.org/10.1093/nar/gkad032

DNA strand breaks are repaired by DNA synthesis from an exposed DNA end paired with a homologous DNA template. DNA polymerase delta (Pol δ) catalyses DNA synthesis in multiple eukaryotic DNA break repair pathways but triggers genome instability unles... Read More about Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing.

SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation (2022)
Journal Article
Winterhalter, C., Stevens, D., Fenyk, S., Pelliciari, S., Marchand, E., Soultanas, P., …Murray, H. (2023). SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation. Nucleic Acids Research, 51(9), 4302-4321. https://doi.org/10.1093/nar/gkac1060

Bidirectional DNA replication from a chromosome origin requires the asymmetric loading of two helicases, one for each replisome. Our understanding of the molecular mechanisms underpinning helicase loading at bacterial chromosome origins is incomplete... Read More about SirA inhibits the essential DnaA:DnaD interaction to block helicase recruitment during Bacillus subtilis sporulation.

Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space (2022)
Journal Article
Okoye, J. C., Bellamy-Carter, J., Oldham, N. J., Oldfield, N. J., Mahdavi, J., & Soultanas, P. (2022). Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space. Computational and Structural Biotechnology Journal, 20, 5355-5363. https://doi.org/10.1016/j.csbj.2022.09.032

Ferric chelates like ferric tyrosinate (TYPLEX) and the closely related ferric quinate (QPLEX) are structural mimics of bacterial siderophores. TYPLEX has been trialled as a feed additive in farming of commercial broilers, reducing Campylobacter load... Read More about Ferric quinate (QPLEX) interacts with the major outer membrane protein (MOMP) of Campylobacter jejuni and enters through the porin channel into the periplasmic space.

Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication (2022)
Journal Article
Horemans, S., Pitoulias, M., Holland, A., Pateau, E., Lechaplais, C., Ekaterina, D., …Janniere, L. (2022). Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication. BMC Biology, 20, Article 87. https://doi.org/10.1186/s12915-022-01278-3

Background: In all living organisms,DNA replication is exquisitely regulated in a wide range of growth conditions to achieve timely and accurate genome duplication prior to cell division. Failures in this regulation cause DNA damage with potentially... Read More about Pyruvate kinase, a metabolic sensor powering glycolysis, drives the metabolic control of DNA replication.

The HelQ human DNA repair helicase utilizes a PWI-like domain for DNA loading through interaction with RPA, triggering DNA unwinding by the HelQ helicase core (2021)
Journal Article
Jenkins, T., Northall, S. J., Ptchelkine, D., Lever, R., Cubbon, A., Betts, H., …Bolt, E. L. (2021). The HelQ human DNA repair helicase utilizes a PWI-like domain for DNA loading through interaction with RPA, triggering DNA unwinding by the HelQ helicase core. NAR Cancer, 3(1), Article zcaa043. https://doi.org/10.1093/narcan/zcaa043

Genome instability is a characteristic enabling factor for carcinogenesis. HelQ helicase is a component of human DNA maintenance systems that prevent or reverse genome instability arising during DNA replication. Here, we provide details of the molecu... Read More about The HelQ human DNA repair helicase utilizes a PWI-like domain for DNA loading through interaction with RPA, triggering DNA unwinding by the HelQ helicase core.

Evaluation of in-field efficacy of dietary ferric tyrosine on performance, intestinal health and meat quality of broiler chickens exposed to natural Campylobacter jejuni challenge (2019)
Journal Article
Skoufos, I., Tzora, A., Giannenas, I., Bonos, E., Tsinas, A., ΜcCartney, Ε., …Soultanas, P. (2019). Evaluation of in-field efficacy of dietary ferric tyrosine on performance, intestinal health and meat quality of broiler chickens exposed to natural Campylobacter jejuni challenge. Livestock Science, 221, 44-51. https://doi.org/10.1016/j.livsci.2019.01.008

Campylobacter is an important pathogen commonly found in chickens that can cause severe acute gastroenteritis in humans. Despite intensive efforts to inhibit food-borne transmission of Campylobacter no effective strategy exists to reduce Campylobacte... Read More about Evaluation of in-field efficacy of dietary ferric tyrosine on performance, intestinal health and meat quality of broiler chickens exposed to natural Campylobacter jejuni challenge.

DNA replication initiation in Bacillus subtilis: Structural and functional characterization of the essential DnaA-DnaD interaction (2018)
Journal Article
Martin, E., Williams, H. E., Pitoulias, M., Stevens, D., Winterhalter, C., Craggs, T. D., …Soultanas, P. (2019). DNA replication initiation in Bacillus subtilis: Structural and functional characterization of the essential DnaA-DnaD interaction. Nucleic Acids Research, 47(4), 2101-2112. https://doi.org/10.1093/nar/gky1220

© 2018 The Author(s). The homotetrameric DnaD protein is essential in low G+C content gram positive bacteria and is involved in replication initiation at oriC and re-start of collapsed replication forks. It interacts with the ubiquitously conserved b... Read More about DNA replication initiation in Bacillus subtilis: Structural and functional characterization of the essential DnaA-DnaD interaction.

Dietary supplementation with ferric tyrosine improves zootechnical performance and reduces caecal Campylobacter spp. load in poultry (2018)
Journal Article
Currie, D., Green, M., Dufailu, O. A., Pitoulias, M., Soultanas, P., McCartney, E., …Mahdavi, J. (2018). Dietary supplementation with ferric tyrosine improves zootechnical performance and reduces caecal Campylobacter spp. load in poultry. British Poultry Science, 59(6), 646-653. https://doi.org/10.1080/00071668.2018.1507015

The objective of this study was to evaluate the effect of ferric tyrosine on the reduction of Campylobacter spp. and zootechnical performance in broilers exposed to Campylobacter spp. using a natural challenge model to simulate commercial conditions.... Read More about Dietary supplementation with ferric tyrosine improves zootechnical performance and reduces caecal Campylobacter spp. load in poultry.

TYPLEX® Chelate, a novel feed additive, inhibits Campylobacter jejuni biofilm formation and cecal colonization in broiler chickens (2018)
Journal Article
Khattak, F., Green, M., Paschalis, V., Houdijk, J., Soultanas, P., & Mahdavi, J. (2018). TYPLEX® Chelate, a novel feed additive, inhibits Campylobacter jejuni biofilm formation and cecal colonization in broiler chickens. Poultry Science, 97(4), https://doi.org/10.3382/ps/pex413

Reducing Campylobacter spp. carriage in poultry is challenging, but essential to control this major cause of human bacterial gastroenteritis worldwide. Although much is known about the mechanisms and route of Campylobacter spp. colonization in poultr... Read More about TYPLEX® Chelate, a novel feed additive, inhibits Campylobacter jejuni biofilm formation and cecal colonization in broiler chickens.

Interactions of the Bacillus subtilis DnaE polymerase with replisomal proteins modulate its activity and fidelity (2017)
Journal Article
Paschalis, V., Le Chatelier, E., Green, M., Képès, F., Soultanas, P., & Janniere, L. (2017). Interactions of the Bacillus subtilis DnaE polymerase with replisomal proteins modulate its activity and fidelity. Open Biology, 7(9), Article 170146. https://doi.org/10.1098/rsob.170146

During Bacillus subtilis replication two replicative polymerases function at the replisome to collectively carry out genome replication. In a reconstituted in vitro replication assay, PolC is the main polymerase while the lagging strand DnaE polymera... Read More about Interactions of the Bacillus subtilis DnaE polymerase with replisomal proteins modulate its activity and fidelity.

DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain (2017)
Journal Article
Northall, S. J., Buckley, R., Jones, N., Penedo, J. C., Soultanas, P., & Bolt, E. L. (2017). DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain. DNA Repair, 57, https://doi.org/10.1016/j.dnarep.2017.07.005

Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in... Read More about DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain.

Primase is required for helicase activity and helicase alters the specificity of primase in the enteropathogen Clostridium difficile (2016)
Journal Article
van Eijk, E., Paschalis, V., Green, M., Friggen, A. H., Larson, M. A., Spriggs, K., …Smits, W. K. (2016). Primase is required for helicase activity and helicase alters the specificity of primase in the enteropathogen Clostridium difficile. Open Biology, 6(12), Article 160272. https://doi.org/10.1098/rsob.160272

DNA replication is an essential and conserved process in all domains of life and may serve as a target for the development of new antimicrobials. However, such developments are hindered by subtle mechanistic differences and limited understanding of D... Read More about Primase is required for helicase activity and helicase alters the specificity of primase in the enteropathogen Clostridium difficile.

Remodeling and control of homologous recombination by DNA helicases and translocases that target recombinases and synapsis (2016)
Journal Article
Northall, S. J., Ivan?i?-Ba?e, I., Soultanas, P., & Bolt, E. L. (2016). Remodeling and control of homologous recombination by DNA helicases and translocases that target recombinases and synapsis. Genes, 7(8), 1-12. https://doi.org/10.3390/genes7080052

Recombinase enzymes catalyse invasion of single-stranded DNA (ssDNA) into homologous duplex DNA forming "Displacement loops" (D-loops), a process called synapsis. This triggers homologous recombination (HR), which can follow several possible paths to... Read More about Remodeling and control of homologous recombination by DNA helicases and translocases that target recombinases and synapsis.

SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance (2016)
Journal Article
Asiani, K. R., Williams, H. E. L., Bird, L., Jenner, M., Searle, M. S., Hobman, J. L., …Soultanas, P. (2016). SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance. Molecular Microbiology, 101(5), 731-742. https://doi.org/10.1111/mmi.13399

Ag+ resistance was initially found on the Salmonella enetrica serovar Typhimurium multi-resistance plasmid pMG101 from burns patients in 1975. The putative model of Ag+ resistance, encoded by the sil operon from pMG101, involves export of Ag+ via an... Read More about SilE is an intrinsically disordered periplasmic ‘molecular sponge' involved in bacterial silver resistance.

Defining the intrinsically disordered C-terminal domain of SSB reveals DNA-mediated compaction (2015)
Journal Article
Green, M., Hatter, L., Brookes, E., Soultanas, P., & Scott, D. (2016). Defining the intrinsically disordered C-terminal domain of SSB reveals DNA-mediated compaction. Journal of Molecular Biology, 428(2), 357-364. https://doi.org/10.1016/j.jmb.2015.12.007

The bacterial single-stranded DNA (ssDNA) binding protein SSB is a strictly conserved and essential protein involved in diverse functions of DNA metabolism, including replication and repair. SSB comprises a well-characterized tetrameric core of N-ter... Read More about Defining the intrinsically disordered C-terminal domain of SSB reveals DNA-mediated compaction.