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PARPin SIGNED

Regulation of (ADP-ribosyl)ation signalling in the DNA damage response: elucidating the function of a novel PARP1/ARTD1 interactor

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EC-Contrib. €

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Project "PARPin" data sheet

The following table provides information about the project.

Coordinator
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD 

Organization address
address: WELLINGTON SQUARE UNIVERSITY OFFICES
city: OXFORD
postcode: OX1 2JD
website: www.ox.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 http://ivanahellab.wixsite.com/ivan-ahel-lab/home
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-03-01   to  2018-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD UK (OXFORD) coordinator 183˙454.00

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 Project objective

(ADP-ribosyl)ation is a dynamic post-translational modification synthesised by PARPs/ARTDs and regulates a diverse array of cellular processes, including the DNA damage response (DDR). The last decade has significantly improved our understanding of the key enzymes involved in (ADP-ribosyl)ation and the cellular pathways they function within. However, our understanding of how these enzymes are regulated is lacking and demands further investigation. In this proposal I seek to redress this. I have provided promising preliminary data identifying a novel uncharacterised interactor of PARP1 involved in the DDR. I expect that this novel protein will have a fundamental role in PARP1 biology in cells given that the two have co-evolved and form a protein complex in cells. I will implement newly available cutting-edge technologies, such as CRISPR-Cas9 and quantitative cell biology approaches, into an interdisciplinary strategy involving genetics, cell biology, structural biology and biochemistry. This strategy will allow me to address the following research objectives: (1) elucidate the function of this protein complex in genome maintenance (2) determine the atomic structure of the complex (3) define the physiological function of the protein complex using genetic mouse models. This timely and holistic approach will allow me to answer crucial outstanding questions related to the regulation of (ADP-ribosyl)ation signalling for the first time. Consequently, this will be the first mechanistic study of its function and therefore my research objectives are likely to yield original insights into novel aspects of (ADP-ribosyl)ation signalling. The objectives described in this proposal will enhance my potential to become an independent investigator by promoting the diversification of my technical competences through training at a world-leading institute and host laboratory. Therefore, the proposal is well aligned with the over-arching aims of the Work Programme.

 Publications

year authors and title journal last update
List of publications.
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 Marion Schuller, Kerstin Riedel, Ian Gibbs-Seymour, Kristin Uth, Christian Sieg, André P. Gehring, Ivan Ahel, Franz Bracher, Benedikt M. Kessler, Jonathan M. Elkins, Stefan Knapp
Discovery of a Selective Allosteric Inhibitor Targeting Macrodomain 2 of Polyadenosine-Diphosphate-Ribose Polymerase 14
published pages: 2866-2874, ISSN: 1554-8929, DOI: 10.1021/acschembio.7b00445
ACS Chemical Biology 12/11 2019-06-13
2016 Christopher J. Staples, Giancarlo Barone, Katie N. Myers, Anil Ganesh, Ian Gibbs-Seymour, Abhijit A. Patil, Ryan D. Beveridge, Caroline Daye, Richard Beniston, Sarah Maslen, Ivan Ahel, J. Mark Skehel, Spencer J. Collis
MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response
published pages: 2565-2575, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.07.087
Cell Reports 16/10 2019-06-13
2016 Ian Gibbs-Seymour, Pietro Fontana, Johannes Gregor Matthias Rack, Ivan Ahel
HPF1/C4orf27 Is a PARP-1-Interacting Protein that Regulates PARP-1 ADP-Ribosylation Activity
published pages: 432-442, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2016.03.008
Molecular Cell 62/3 2019-06-13
2018 Dominika Kwasna, Syed Arif Abdul Rehman, Jayaprakash Natarajan, Stephen Matthews, Ross Madden, Virginia De Cesare, Simone Weidlich, Satpal Virdee, Ivan Ahel, Ian Gibbs-Seymour, Yogesh Kulathu
Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability
published pages: , ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.02.023
Molecular Cell 2019-06-13

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