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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.

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

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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