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3D-REPAIR SIGNED

Spatial organization of DNA repair within the nucleus

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

3D-REPAIR project word cloud

Explore the words cloud of the 3D-REPAIR project. It provides you a very rough idea of what is the project "3D-REPAIR" about.

detection nuclear recurrent kinetics resolution locus unravel coupled nucleotide preserve 3d mutagenic structure cells dsbs faithful environment dsb origin tethering nucleus quantitative translocations double specificity breaks instability folding regions proteomics structures organization single orchestrated implications mapping activated unknown induction dna susceptible cancer time locations regulated tightly integrity mechanisms determines signaling reveal compartmentalization chromatin spatial architecture frequency genomic nevertheless efficiency certain compartments protein completely stranded maps dictated cas9 balance heterochromatin mutations chromosomal topological genome shown first random biotinylation repair crispr understand promiscuous

Project "3D-REPAIR" data sheet

The following table provides information about the project.

Coordinator	THE UNIVERSITY OF SUSSEX Organization address address: SUSSEX HOUSE FALMER city: BRIGHTON postcode: BN1 9RH website: http://www.sussex.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://www.igbmc.fr/research/department/1/team/28/
Total cost	1˙999˙750 €
EC max contribution	1˙999˙750 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2015-CoG
Funding Scheme	ERC-COG
Starting year	2017
Duration (year-month-day)	from 2017-03-01 to 2022-02-28

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	THE UNIVERSITY OF SUSSEX THE UNIVERSITY OF SUSSEX Organization address address: SUSSEX HOUSE FALMER city: BRIGHTON postcode: BN1 9RH website: http://www.sussex.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.	UK (BRIGHTON)	coordinator	776˙220.00
2	CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE Organization address address: Rue Laurent Fries 1 city: ILLKIRCH GRAFFENSTADEN postcode: 67404 website: www.igbmc.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (ILLKIRCH GRAFFENSTADEN)	participant	1˙223˙529.00

Map

Project objective

Faithful repair of double stranded DNA breaks (DSBs) is essential, as they are at the origin of genome instability, chromosomal translocations and cancer. Cells repair DSBs through different pathways, which can be faithful or mutagenic, and the balance between them at a given locus must be tightly regulated to preserve genome integrity. Although, much is known about DSB repair factors, how the choice between pathways is controlled within the nuclear environment is not understood. We have shown that nuclear architecture and non-random genome organization determine the frequency of chromosomal translocations and that pathway choice is dictated by the spatial organization of DNA in the nucleus. Nevertheless, what determines which pathway is activated in response to DSBs at specific genomic locations is not understood. Furthermore, the impact of 3D-genome folding on the kinetics and efficiency of DSB repair is completely unknown. Here we aim to understand how nuclear compartmentalization, chromatin structure and genome organization impact on the efficiency of detection, signaling and repair of DSBs. We will unravel what determines the DNA repair specificity within distinct nuclear compartments using protein tethering, promiscuous biotinylation and quantitative proteomics. We will determine how DNA repair is orchestrated at different heterochromatin structures using a CRISPR/Cas9-based system that allows, for the first time robust induction of DSBs at specific heterochromatin compartments. Finally, we will investigate the role of 3D-genome folding in the kinetics of DNA repair and pathway choice using single nucleotide resolution DSB-mapping coupled to 3D-topological maps. This proposal has significant implications for understanding the mechanisms controlling DNA repair within the nuclear environment and will reveal the regions of the genome that are susceptible to genomic instability and help us understand why certain mutations and translocations are recurrent in cancer

Publications

List of publications.
year	authors and title	journal	last update
2016	Katerina Tsouroula, Audrey Furst, Melanie Rogier, Vincent Heyer, Anne Maglott-Roth, Alexia Ferrand, Bernardo Reina-San-Martin, Evi Soutoglou Temporal and Spatial Uncoupling of DNA Double Strand Break Repair Pathways within Mammalian Heterochromatin published pages: 293-305, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2016.06.002	Molecular Cell 63/2	2020-01-20

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