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DUT-signal SIGNED

dUTPase Signalling: from Phage to Eukaryotes

Total Cost €

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EC-Contrib. €

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Partnership

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 DUT-signal project word cloud

Explore the words cloud of the DUT-signal project. It provides you a very rough idea of what is the project "DUT-signal" about.

transfer    unsolved    acts    enzymes    de    disorders    mechanistic    pathogenicity    ground    repression    generates    cycle    levels    supporting    region    demonstrated    interacts    stems    possess    uracil    contrast    breaking    functions    sapi    misincorporation    phage    transcriptional    entirely    regulatory    domain    trimeric    encoded    messenger    dutpases    stl    group    regulate    mechanism    conformation    dutp    apo    elucidation    eukaryotic    orders    summary    protein    unable    sapis    alpha    domains    signalling    duts    bound    rat    rendering    biological    islands    dut    binding    potentially    revealed    hydrolysis    family    prevent    molecules    suffice    unexpectedly    proteins    surprising    induce    conversion    conserved    contribution    strategy    interaction    vi    dna    opening    ppar    motif    extra    staphylococcal    suggest    terminal    possibility    depends    crystallographic    cellular    repressor    mutagenic    inherently    mediating    analogously   

Project "DUT-signal" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF GLASGOW 

Organization address
address: UNIVERSITY AVENUE
city: GLASGOW
postcode: G12 8QQ
website: www.gla.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://www.gla.ac.uk/researchinstitutes/iii/staff/joserpenades/
 Total cost 2˙246˙192 €
 EC max contribution 2˙246˙192 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-12-01   to  2020-11-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF GLASGOW UK (GLASGOW) coordinator 2˙246˙192.00

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 Project objective

dUTPases (DUTs) are enzymes that regulate cellular dUTP levels to prevent the misincorporation of uracil into DNA. Recently however, DUTs have been involved in the control of relevant cellular processes. How these regulatory functions are controlled remains unsolved. The recent elucidation of the mechanistic role of DUTs in the transfer of staphylococcal pathogenicity islands (SaPIs) by our group has revealed an entirely novel and surprising strategy involving DUTs in signalling. Namely, we have demonstrated that in addition to the 5 classical domains present in all the trimeric DUTs, staphylococcal phage-encoded DUT proteins possess an extra region (Motif VI) involved in SaPI de-repression by binding to the SaPI-encoded repressor (Stl). Although this domain is necessary, it does not suffice to induce the SaPI cycle. Unexpectedly, the strongly conserved DUT motif V is also inherently involved in mediating de-repression. Crystallographic and mutagenic analyses have demonstrated that binding to dUTP orders the C-terminal motif V of phage-encoded DUTs, potentially rendering these proteins in the conformation required for SaPI de-repression. In contrast, conversion into the apo state conformation by the hydrolysis of the bound dUTP disorders motif V and generates a protein that is unable to induce the SaPI cycle. Analogously, previous work demonstrated that the trimeric rat DUT interacts with the transcriptional factor PPARα, an interaction that depends on an “extra” N-terminal motif VI present in the DUT protein and requires the C-terminal domain contribution, strongly supporting in general the mechanism involving DUTs in signalling. In summary, our results suggest that DUTs define a widespread family of signalling molecules that acts analogously to eukaryotic G-proteins. This project stems from this ground-breaking result, and will investigate the biological role of DUTs as signalling molecules, opening up the possibility to establish dUTP as a new second messenger.

 Publications

year authors and title journal last update
List of publications.
2019 Francisca Gallego del Sol, José R. Penadés, Alberto Marina
Deciphering the Molecular Mechanism Underpinning Phage Arbitrium Communication Systems
published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.01.025
Molecular Cell 2020-04-07
2018 John Chen, Nuria Quiles-Puchalt, Yin Ning Chiang, Rodrigo Bacigalupe, Alfred Fillol-Salom, Melissa Su Juan Chee, J. Ross Fitzgerald, José R. Penadés
Genome hypermobility by lateral transduction
published pages: 207-212, ISSN: 0036-8075, DOI: 10.1126/science.aat5867
Science 362/6411 2020-04-07
2018 Alfred Fillol-Salom, Roser Martínez-Rubio, Rezheen F. Abdulrahman, John Chen, Robert Davies, José R. Penadés
Phage-inducible chromosomal islands are ubiquitous within the bacterial universe
published pages: 2114-2128, ISSN: 1751-7362, DOI: 10.1038/s41396-018-0156-3
The ISME Journal 12/9 2020-04-07
2017 Janine Bowring, Maan M Neamah, Jorge Donderis, Ignacio Mir-Sanchis, Christian Alite, J Rafael Ciges-Tomas, Elisa Maiques, Iltyar Medmedov, Alberto Marina, José R Penadés
Pirating conserved phage mechanisms promotes promiscuous staphylococcal pathogenicity island transfer
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.26487
eLife 6 2020-04-07
2016 Elisa Maiques, Nuria Quiles-Puchalt, Jorge Donderis, J. Rafael Ciges-Tomas, Christian Alite, Janine Z. Bowring, Suzanne Humphrey, José R. Penadés, Alberto Marina
Another look at the mechanism involving trimeric dUTPases in Staphylococcus aureus pathogenicity island induction involves novel players in the party
published pages: 5457-5469, ISSN: 0305-1048, DOI: 10.1093/nar/gkw317
Nucleic Acids Research 44/11 2020-04-07
2017 Maan M. Neamah, Ignacio Mir-Sanchis, María López-Sanz, Sonia Acosta, Ignacio Baquedano, Andreas F. Haag, Alberto Marina, Silvia Ayora, José R. Penadés
Sak and Sak4 recombinases are required for bacteriophage replication in Staphylococcus aureus
published pages: 6507-6519, ISSN: 0305-1048, DOI: 10.1093/nar/gkx308
Nucleic Acids Research 45/11 2020-04-07
2017 Jorge Donderis, Janine Bowring, Elisa Maiques, J. Rafael Ciges-Tomas, Christian Alite, Iltyar Mehmedov, María Angeles Tormo-Mas, José R. Penadés, Alberto Marina
Convergent evolution involving dimeric and trimeric dUTPases in pathogenicity island mobilization
published pages: e1006581, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006581
PLOS Pathogens 13/9 2020-04-07
2016 Nuria Carpena, Keith A. Manning, Terje Dokland, Alberto Marina, José R. Penadés
Convergent evolution of pathogenicity islands in helper cos phage interference
published pages: 20150505, ISSN: 0962-8436, DOI: 10.1098/rstb.2015.0505
Philosophical Transactions of the Royal Society B: Biological Sciences 371/1707 2020-04-07
2017 Christian Alite, Suzanne Humphrey, Jordi Donderis, Elisa Maiques, J. Rafael Ciges-Tomas, José R. Penadés, Alberto Marina
Dissecting the link between the enzymatic activity and the SaPI inducing capacity of the phage 80α dUTPase
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-11234-9
Scientific Reports 7/1 2020-04-07

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