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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.

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

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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