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3D-loop SIGNED

Mechanism of homology search and the logic of homologous chromosome pairing in meiosis

Total Cost €

0

EC-Contrib. €

0

Partnership

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 3D-loop project word cloud

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

homologs    conundrums    lasting    suite    core    uniquely    achieves    detect    capacity    fundamental    builds    chromosome    tackle    homolog    conserved    cis    dynamics    sexual    synthesis    identification    repair    purpose    accurate    reproduction    overcame    loop    recombination    region    donor    involvement    elaborate    regulation    ssdna    basis    uses    hurdle    dna    integrates    phenomenon    shed    molecule    regulations    nucleus    sampling    yeast    efficient    search    molecules    cartography    quantitative    dsb    acting    single    paradigm    strand    proximity    molecular    assembled    breaks    chromosomal    genome    joint    revealed    pairing    mechanism    ligation    homology    dynamic    hr    wp2    first    revisit    events    class    template    framework    associates    re    engineering    nucleoprotein    basic    flanking    double    probe    harnessed    wp1    vastness    experimental    npf    intact    cells    cytological    lying    3d    meiosis    physically    mitotic    light    filament    crossover    homologous    attachment   

Project "3D-loop" 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 1˙499˙779 €
 EC max contribution 1˙499˙779 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2020
 Duration (year-month-day) from 2020-01-01   to  2024-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 1˙499˙779.00

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 Project objective

Homologous recombination (HR) is a conserved DNA double-strand breaks (DSB) repair pathway that uniquely uses an intact DNA molecule as a template. Genome-wide homology search is carried out by a nucleoprotein filament (NPF) assembled on the ssDNA flanking the DSB, and whose product is a “D-loop” joint molecule. Beyond accurate DSB repair, this capacity of HR to spatially associates homologous molecules is also harnessed for homolog pairing in meiosis. The goal of “3D-loop” is to tackle two long lasting conundrums: the fundamental homology search mechanism that achieves accurate and efficient identification of a single homologous donor in the vastness of the genome and nucleus, and how this mechanism is adapted for the purpose of homologs attachment in meiosis. I overcame the main hurdle to study these core steps of HR by developing a suite of proximity ligation-based methodologies and experimental systems to physically detect joint molecules in yeast cells. It revealed elaborate regulation controlling D-loop dynamics and a novel class of joint molecules. This proposal builds upon these methodologies and findings to first address basic properties of the homology sampling process by the NPF and the role of D-loop dynamics, with the long-term goal to establish a quantitative framework of homology search in mitotic cells (WP1). Second, the meiosis-specific regulation of homology search leading to homolog pairing likely integrates chromosomal-scale information. Genome re-synthesis and engineering approaches will be deployed to (i) achieve a quantitative and dynamic cartography of the cytological and molecular events of meiosis over a large chromosomal region, (ii) probe cis-acting regulations at the chromosomal scale, and (iii) revisit the molecular paradigm for crossover formation (WP2). We expect this project to shed light on the fundamental process of homology search and its involvement in the chromosome pairing phenomenon lying at the basis of sexual reproduction.

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