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Cryo-EM Imaging of Histone Recycling at the Replication Fork

Total Cost €


EC-Contrib. €






 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.

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

Project "Cryo-H-Rec" data sheet

The following table provides information about the project.


Organization address
address: 1 MIDLAND ROAD
city: LONDON
postcode: NW1 1AT

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


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 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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