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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. €

0

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.

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

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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