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DIvA SIGNED

Chromatin function in DNA Double Strand breaks repair: Prime, repair and restore DSB Inducible via AsiSI

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Project "DIvA" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

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 France [FR]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 2˙000˙000.00

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 Project objective

'Among the types of damage, DNA Double Strands Breaks (DSBs) are the most deleterious, as illustrated by the variety of human diseases associated with DSB repair defects. Repair of DSB into the chromatin context raises several questions that we aim to address in this proposal. Firstly, it is likely that the chromatin environment where a break occurs influences the choice of repair pathway. Since the different DSB repair mechanisms can lead to different 'scar' on the genome, further studies are required to elucidate how chromatin structure regulates the targeting of DSB repair machineries. Secondly, DNA packaging into chromatin hinders detection and repair of DSBs and many chromatin modifications were recently identified as induced around DSBs to facilitate repair. However, a complete picture of the chromatin landscape set up at DSB, and more specifically the set of histone modifications associated with each repair pathway ('repair histone code') is still awaited. In addition, whether and how damaged chromosomes are reorganized within the nucleus is still unknown. Finally, once repair has been completed, the initial chromatin landscape must be faithfully restored in order to maintain epigenome stability and cell fate. Using an experimental system we recently developed (called DIvA for DSB Inducible via AsiSI), that allows the induction of multiple sequence-specific DSBs widespread across the genome, we propose to investigate these uncovered aspects of the relationship between chromatin and DSB repair. By high-throughput genomic and proteomic technologies, we will try (i) to understand the contribution of chromatin in the DSB repair pathway choice (PRIME), (ii) to describe more thoroughly the chromatin remodeling events and the spatial chromosomes reorganization, that occur concomitantly to DSB to promote adequate repair (REPAIR), and (iii) to elucidate the processes at work to restore epigenome integrity after DSB repair (RESTORE). '

 Publications

year authors and title journal last update
List of publications.
2017 Aude Guénolé, Gaëlle Legube
A meeting at risk: Unrepaired DSBs go for broke
published pages: 589-599, ISSN: 1949-1034, DOI: 10.1080/19491034.2017.1380138
Nucleus 8/6 2020-03-20
2017 Thomas Clouaire, Aline Marnef, Gaëlle Legube
Taming Tricky DSBs: ATM on duty
published pages: 84-91, ISSN: 1568-7864, DOI: 10.1016/j.dnarep.2017.06.010
DNA Repair 56 2020-03-20
2017 François Aymard, Marion Aguirrebengoa, Emmanuelle Guillou, Biola M Javierre, Beatrix Bugler, Coline Arnould, Vincent Rocher, Jason S Iacovoni, Anna Biernacka, Magdalena Skrzypczak, Krzysztof Ginalski, Maga Rowicka, Peter Fraser, Gaëlle Legube
Genome-wide mapping of long-range contacts unveils clustering of DNA double-strand breaks at damaged active genes
published pages: 353-361, ISSN: 1545-9993, DOI: 10.1038/nsmb.3387
Nature Structural & Molecular Biology 24/4 2020-03-20
2018 Sarah Cohen, Nadine Puget, Yea-Lih Lin, Thomas Clouaire, Marion Aguirrebengoa, Vincent Rocher, Philippe Pasero, Yvan Canitrot, Gaëlle Legube
Senataxin resolves RNA:DNA hybrids forming at DNA double-strand breaks to prevent translocations
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-02894-w
Nature Communications 9/1 2020-03-20
2015 Pierre Caron, Jonathan Choudjaye, Thomas Clouaire, Béatrix Bugler, Virginie Daburon, Marion Aguirrebengoa, Thomas Mangeat, Jason S. Iacovoni, Alejandro Álvarez-Quilón, Felipe Cortés-Ledesma, Gaëlle Legube
Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks
published pages: 1598-1609, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2015.10.024
Cell Reports 13/8 2020-03-20
2015 Francois Aymard, Gaëlle Legube
A TAD closer to ATM
published pages: e1134411, ISSN: 2372-3556, DOI: 10.1080/23723556.2015.1134411
Molecular & Cellular Oncology 3/3 2020-03-20

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