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Cryo-H-Rec SIGNED

Cryo-EM Imaging of Histone Recycling at the Replication Fork

Total Cost €

0

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.

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

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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