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InVivo_DDR_ADPR SIGNED

Decoding the DNA damage signalling in C. elegans by proteomic analyses of ADP-ribosylation

Total Cost €

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EC-Contrib. €

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Partnership

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 InVivo_DDR_ADPR project word cloud

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

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Project "InVivo_DDR_ADPR" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: Munich
postcode: 80539
website: www.mpg.de

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

 Coordinator Country Germany [DE]
 Project website https://www.age.mpg.de/science/research-labs/matic/
 Total cost 159˙460 €
 EC max contribution 159˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2018-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 159˙460.00

Map

 Project objective

Preservation of genome integrity and stability is critical for survival and propagation of individuals and species. Organisms have thus evolved rapid and efficient mechanisms -collectively termed the DNA damage response (DDR)- to combat threats posed by DNA damage. Among these, the post-translational modification (PTM) ADP-ribosylation (ADPR) plays a decisive role in effective DDR. Although much is known about the relevance of ADPR upon DNA injury, the underlying molecular mechanisms are still poorly understood and no systematic, unbiased proteome-wide study to determine ADPR targets in vivo has been conducted to date. The most challenging and innovative goal of this proposal is to profile in vivo ADP-ribosylated peptides during DDR in the well-established model system Caenorhabditis elegans by the combined application of advanced proteomic approaches. I will develop novel enrichment strategies that will allow me to confidently map for the first time all the sites of ADPR throughout the C. elegans proteome. I will take advantage of SILAN technology, which allows stable isotope labelling in C. elegans, to determine the quantitative profiles of thousands of ADPR sites during DDR. By bioinformatic analysis, I will select candidate proteins for further investigation of the biological role of DNA damage-induced ADPR. I will then test the biological impact of ADPR of these candidates through site-specific mutation of their identified modification sites. Finally, I will perform biochemical, molecular and functional experiments to study how ADPR alters the activity of these proteins and thereby characterize the mode of ADPR action. Understanding the regulatory networks that underlie such a complex biological process at the organism level will provide new insights for improved treatment of DNA damage-related diseases including cancer. This is an ambitious, innovative, cross-disciplinary project at the forefront of two exciting fields, biology and proteomics.

 Publications

year authors and title journal last update
List of publications.
2017 Alisa Zhiteneva, Juan Jose Bonfiglio, Alexandr Makarov, Thomas Colby, Paola Vagnarelli, Eric C. Schirmer, Ivan Matic, William C. Earnshaw
Mitotic post-translational modifications of histones promote chromatin compaction in vitro
published pages: 170076, ISSN: 2046-2441, DOI: 10.1098/rsob.170076
Open Biology 7/9 2019-06-13
2016 Orsolya Leidecker, Juan José Bonfiglio, Thomas Colby, Qi Zhang, Ilian Atanassov, Roko Zaja, Luca Palazzo, Anna Stockum, Ivan Ahel, Ivan Matic
Serine is a new target residue for endogenous ADP-ribosylation on histones
published pages: 998-1000, ISSN: 1552-4450, DOI: 10.1038/nchembio.2180
Nature Chemical Biology 12/12 2019-06-13
2017 Pietro Fontana, Juan José Bonfiglio, Luca Palazzo, Edward Bartlett, Ivan Matic, Ivan Ahel
Serine ADP-ribosylation reversal by the hydrolase ARH3
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.28533
eLife 6 2019-06-13
2017 Juan José Bonfiglio, Pietro Fontana, Qi Zhang, Thomas Colby, Ian Gibbs-Seymour, Ilian Atanassov, Edward Bartlett, Roko Zaja, Ivan Ahel, Ivan Matic
Serine ADP-Ribosylation Depends on HPF1
published pages: 932-940.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.01.003
Molecular Cell 65/5 2019-06-13
2017 Juan J. Bonfiglio, Thomas Colby, Ivan Matic
Mass spectrometry for serine ADP-ribosylation? Think o-glycosylation!
published pages: 6259-6264, ISSN: 0305-1048, DOI: 10.1093/nar/gkx446
Nucleic Acids Research 45/11 2019-06-13

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