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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.

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

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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