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Cryo-H-Rec SIGNED

Cryo-EM Imaging of Histone Recycling at the Replication Fork

Total Cost €

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EC-Contrib. €

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Partnership

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 Cryo-H-Rec project word cloud

Explore the words cloud of the Cryo-H-Rec project. It provides you a very rough idea of what is the project "Cryo-H-Rec" about.

recycling    transmission    elucidate    disassembly    activation    protects    structural    describe    regulating    controls    nucleosome    characterise    density    modulates    histones    capture    complementary    marks    material    spectroscopy    nmr    chromatinised    intermediate    cell    code    densely    strands    perform    histone    duplication    resort    fork    eukaryotic    spectrometry    crosslinking    silencing    machinery    intend    genetic    organisation    arrays    parental    molecular    reshuffling    synthesized    components    xl    chromatin    daughter    regions    concerted    modifications    reassembles    array    dna    chromosomal    chromosome    packaged    template    duplicate    pivotal    intermediates    nascent    subject    gene    mechanism    electron    cells    inheritance    dismantles    seek    microscopy    multidisciplinary    replisome    form    unravel    proteins    proliferation    duplicated    newly    ahead    ptms    em    underpins    ms    post    dissect    nucleosomes    solution    incorporation    mass    techniques    image    expression    reconstitution    maintaining    epigenetic    cryo    redeposition    translational    vitro    replication    employ   

Project "Cryo-H-Rec" 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 212˙933 €
 EC max contribution 212˙933 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 212˙933.00

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 Project objective

DNA replication is essential for cell proliferation. In eukaryotic cells, DNA is densely packaged in nucleosome arrays that form chromatin. Such organisation protects the genetic material and controls access to DNA, thus providing an important mechanism for regulating gene expression. The eukaryotic replication machinery has evolved to unravel nucleosomes in order to access and duplicate DNA, while also maintaining chromatin density on newly duplicated DNA. To achieve this, the replisome dismantles nucleosomes ahead of the replication fork and reassembles them on nascent DNA strands, by coordinating redeposition of parental and newly synthesized histones. Histone proteins are subject to an array of post-translational modifications (PTMs), providing an epigenetic code that modulates activation and silencing of specific chromosomal regions. Redeposition of parental histones with their PTMs on both nascent DNA strands is, thus, pivotal in transmission of the epigenetic marks to daughter cells. I intend to perform in vitro reconstitution of the replisome on a chromatinised template and use cryo-electron microscopy to image DNA duplication and parental histone recycling at the replication fork. I seek to describe different structural intermediates in the process of nucleosome disassembly, DNA duplication and histone incorporation into new nucleosomes. To capture and characterise intermediate states of the replication machinery during this concerted process, I will employ a multidisciplinary approach and resort to structural techniques complementary to cryo-EM like solution NMR spectroscopy and crosslinking-mass spectrometry (XL-MS). My results will help dissect the role of different replisome components in nucleosome reshuffling at the replication fork, and elucidate the molecular mechanism that underpins chromosome replication and epigenetic inheritance.

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The information about "CRYO-H-REC" are provided by the European Opendata Portal: CORDIS opendata.

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