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CRYOREP SIGNED

Chromosome Replication Visualised by Cryo-EM

Total Cost €

0

EC-Contrib. €

0

Partnership

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 CRYOREP project word cloud

Explore the words cloud of the CRYOREP project. It provides you a very rough idea of what is the project "CRYOREP" about.

argue    protocols    chromosome    origin    errors    regulate    events    natural    performed    experiments    cellular    helicase    basis    movie    understand    initiation    cell    genetic    eject    untwisting    genomic    compact    reconstitution    mcm    frozen    image    simplified    cryo    linear    stimulating    roles    polymerases    structural    electron    plays    progression    activators    achievements    microscope    loading    substrate    cancer    dna    fork    ring    onset    once    imaging    forks    genome    chromatin    abnormalities    machinery    catalysed    duplication    recruited    instability    stability    strategies    regulated    tightly    strand    firing    linked    investigations    templates    dictating    unwinding    interaction    sites    ploidy    opens    entire    regulatory    arrays    first    inactive    disease    propagation    proteins    mechanisms    think    formed    visual    double    cycle    isolated    reaction    cells    encircles    biochemistry    molecular    perform    replicative    causing    duplex    generate    site    revealed    start    duplicated    replication    nucleosome    purified    artificially    eukaryotic    resolution    motor    helix   

Project "CRYOREP" data sheet

The following table provides information about the project.

Coordinator
THE FRANCIS CRICK INSTITUTE LIMITED 

Organization address
address: 1 MIDLAND ROAD
city: LONDON
postcode: NW1 1AT
website: www.crick.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]
 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-2018-COG
 Funding Scheme ERC-COG
 Starting year 2019
 Duration (year-month-day) from 2019-03-01   to  2024-02-29

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 2˙000˙000.00

Map

 Project objective

In eukaryotic cells, DNA replication is tightly regulated to ensure that the genome is duplicated only once per cell cycle. Errors in the control mechanisms that regulate chromosome ploidy cause genomic instability, which is linked to the development of cellular abnormalities, genetic disease and the onset of cancer. Recent reconstitution experiments performed with purified proteins revealed that initiation of eukaryotic genome duplication requires three distinct steps. First, DNA replication start sites are identified and targeted for the loading of an inactive MCM helicase motor, which encircles the double helix. Second, MCM activators are recruited, causing duplex-DNA untwisting. Third, upon interaction with a firing factor, the MCM ring opens to eject one DNA strand, leading to unwinding of the replication fork and duplication by dedicated replicative polymerases. These three events are not understood at a molecular level. Structural investigations so far aimed at imaging artificially isolated replication steps and used simplified templates, such as linear duplex DNA to study helicase loading or pre-formed forks to understand unwinding. However, the natural substrate of the eukaryotic replication machinery is not DNA but rather chromatin, formed of nucleosome arrays that compact the genome. Chromatin plays important regulatory roles in all steps of DNA replication, by dictating origin start-site selection and stimulating replication fork progression. Only by studying chromatin replication, we argue, will we understand the molecular basis of genome propagation. To this end, we have developed new protocols to perform visual biochemistry experiments under the cryo-electron microscope, to image chromatin duplication at high resolution, frozen as it is being catalysed. Using these strategies we want to generate a molecular movie of the entire replication reaction. Our achievements will change the way we think about genome stability in eukaryotic cells.

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The information about "CRYOREP" are provided by the European Opendata Portal: CORDIS opendata.

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