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CRYOREP SIGNED

Chromosome Replication Visualised by Cryo-EM

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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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.

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

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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