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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.

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

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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