Explore the words cloud of the DUT-signal project. It provides you a very rough idea of what is the project "DUT-signal" about.
The following table provides information about the project.
Coordinator |
UNIVERSITY OF GLASGOW
Organization address contact info |
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 |
Take a look of project's partnership.
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1 | UNIVERSITY OF GLASGOW | UK (GLASGOW) | coordinator | 2˙246˙192.00 |
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.
year | authors and title | journal | last update |
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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 MartÃnez-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, MarÃa 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, MarÃa 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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