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CHROMOREP SIGNED

Reconstitution of Chromosome Replication and Epigenetic Inheritance

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EC-Contrib. €

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Project "CHROMOREP" 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
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name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://www.crick.ac.uk/research/a-z-researchers/
 Total cost 1˙983˙019 €
 EC max contribution 1˙983˙019 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2015
 Duration (year-month-day) from 2015-11-01   to  2020-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 1˙983˙019.00

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 Project objective

A PubMed search for ‘epigenetic’ identifies nearly 35,000 entries, yet the molecular mechanisms by which chromatin modification and gene expression patterns are actually inherited during chromosome replication — mechanisms which lie at the heart of epigenetic inheritance of gene expression — are still largely uncharacterised. Understanding these mechanisms would be greatly aided if we could reconstitute the replication of chromosomes with purified proteins. The past few years have seen great progress in understanding eukaryotic DNA replication through the use of cell-free replication systems and reconstitution of individual steps in replication with purified proteins and naked DNA. We will use these in vitro replication systems together with both established and novel chromatin assembly systems to understand: a) how chromatin influences replication origin choice and timing, b) how nucleosomes on parental chromosomes are disrupted during replication and are distributed to daughter chromatids, and c) how chromatin states and gene expression patterns are re-established after passage of the replication fork. We will begin with simple, defined templates to learn basic principles, and we will use this knowledge to reconstitute genome-wide replication patterns. The experimental plan will exploit our well-characterised yeast systems, and where feasible explore these questions with human proteins. Our work will help explain how epigenetic inheritance works at a molecular level, and will complement work in vivo by many others. It will also underpin our long-term research goals aimed at making functional chromosomes from purified, defined components to understand how DNA replication interacts with gene expression, DNA repair and chromosome segregation.

 Publications

year authors and title journal last update
List of publications.
2017 Jin Chuan Zhou, Agnieszka Janska, Panchali Goswami, Ludovic Renault, Ferdos Abid Ali, Abhay Kotecha, John F. X. Diffley, Alessandro Costa
CMG–Pol epsilon dynamics suggests a mechanism for the establishment of leading-strand synthesis in the eukaryotic replisome
published pages: 4141-4146, ISSN: 0027-8424, DOI: 10.1073/pnas.1700530114
Proceedings of the National Academy of Sciences 114/16 2019-07-04
2017 Joseph T.P. Yeeles, Agnieska Janska, Anne Early, John F.X. Diffley
How the Eukaryotic Replisome Achieves Rapid and Efficient DNA Replication
published pages: 105-116, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2016.11.017
Molecular Cell 65/1 2019-07-04
2018 Max E. Douglas, Ferdos Abid Ali, Alessandro Costa, John F. X. Diffley
The mechanism of eukaryotic CMG helicase activation
published pages: 265-268, ISSN: 0028-0836, DOI: 10.1038/nature25787
Nature 555/7695 2019-07-04
2017 Ferdos Abid Ali, Max E. Douglas, Julia Locke, Valerie E. Pye, Andrea Nans, John F. X. Diffley, Alessandro Costa
Cryo-EM structure of a licensed DNA replication origin
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-017-02389-0
Nature Communications 8/1 2019-07-04
2017 Gideon Coster, John F. X. Diffley
Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading
published pages: 314-318, ISSN: 0036-8075, DOI: 10.1126/science.aan0063
Science 357/6348 2019-07-04
2017 Jordi Frigola, Jun He, Kerstin Kinkelin, Valerie E. Pye, Ludovic Renault, Max E. Douglas, Dirk Remus, Peter Cherepanov, Alessandro Costa, John F. X. Diffley
Cdt1 stabilizes an open MCM ring for helicase loading
published pages: 15720, ISSN: 2041-1723, DOI: 10.1038/ncomms15720
Nature Communications 8 2019-07-04
2017 Christoph F. Kurat, Joseph T.P. Yeeles, Harshil Patel, Anne Early, John F.X. Diffley
Chromatin Controls DNA Replication Origin Selection, Lagging-Strand Synthesis, and Replication Fork Rates
published pages: 117-130, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2016.11.016
Molecular Cell 65/1 2019-07-04

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