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DNA2REPAIR SIGNED

DNA strand break repair and links to human disease

Total Cost €

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EC-Contrib. €

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Partnership

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 DNA2REPAIR project word cloud

Explore the words cloud of the DNA2REPAIR project. It provides you a very rough idea of what is the project "DNA2REPAIR" about.

mechanisms    slx4    understand    apraxia    species    forefront    microscopic    area    assembly    chemicals    thereby    carcinogenic    biochemical    aoa2    employ    integrity    action    oxidative    mechanism    oculomotor    genome    damage    basic    individuals    therapeutic    disorder    breast    breakdown    variety    mus81    inter    structure    forks    slx1    direct    protecting    filament    environment    genetic    eme1    roles    defective    xpf    replication    ercc1    interplay    reactive    tumour    resolution    material    crosslink    sources    either    selective    maintenance    continually    genetically    cancers    repair    senataxin    underpin    erc    neuronal    cancer    diseases    unfortunately    emphasis    ataxia    picture    palb2    radiation    electron    biological    aoa    afflicted    metabolism    crippling    suppressor    ionising    our    dna    anemia    agents    oxygen    made    cells    genes    recognise    instability    rad51    cope    contributions    brca2    endogenous    paralogs    elaborate    rad51ap1    tri    nuclease    fanconi    actions    subjected    predisposed    inheritable    mutations    lesions    neurodegenerative    cell   

Project "DNA2REPAIR" 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 2˙203˙153 €
 EC max contribution 2˙203˙153 € (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 2015-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 2˙203˙153.00

Map

 Project objective

Our genetic material is continually subjected to damage, either from endogenous sources such as reactive oxygen species, produced as by-products of oxidative metabolism, from the breakdown of replication forks during cell growth, or by agents in the environment such as ionising radiation or carcinogenic chemicals. To cope with DNA damage, cells employ elaborate and effective repair processes that specifically recognise a wide variety of lesions in DNA. These repair systems are essential for the maintenance of genome integrity. Unfortunately, some individuals are genetically predisposed to crippling diseases or cancers that are the direct result of mutations in genes involved in the DNA damage response. For several years our work has been at the forefront of basic biological research in the area of DNA repair, and in particular we have made significant contributions to the understanding of inheritable diseases such as breast cancer, Fanconi anemia, and the neurodegenerative disorder Ataxia with Oculomotor Apraxia (AOA). The focus of this ERC proposal is: (i) to determine the mechanism of action and high-resolution structure of the BRCA2 tumour suppressor, and to provide a detailed picture of the interplay between BRCA2, PALB2, RAD51AP1 and the RAD51 paralogs, in terms of RAD51 filament assembly, using biochemical, electron microscopic and cell biological approaches, (ii) to determine the biological role of a unique structure-selective tri-nuclease complex (SLX1-SLX4-MUS81-EME1-XPF-ERCC1), with particular emphasis on its roles in DNA crosslink repair and Fanconi anemia, and (iii) to understand the actions of Senataxin, which is defective in AOA2, in protecting against genome instability in neuronal cells. These three distinct and yet inter-related areas of the research programme will provide an improved understanding of basic mechanisms of DNA repair and thereby underpin future therapeutic developments that will help individuals afflicted with these diseases.

 Publications

year authors and title journal last update
List of publications.
2015 Ying Wai Chan, Stephen West
GEN1 promotes Holliday junction resolution by a coordinated nick and counter-nick mechanism
published pages: 10882-10892, ISSN: 0305-1048, DOI: 10.1093/nar/gkv1207
Nucleic Acids Research 43/22 2020-02-12
2016 Kotynkova, K. Su, K. C. West, S. C. Petronczki, M.
Plasma Membrane Association but Not Midzone Recruitment of RhoGEF ECT2 Is Essential for Cytokinesis
published pages: 2672-2686, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.11.029
Cell Reports 17 2020-02-12
2018 Ying Wai Chan, Kasper Fugger, Stephen C. West
Unresolved recombination intermediates lead to ultra-fine anaphase bridges, chromosome breaks and aberrations
published pages: 92-103, ISSN: 1465-7392, DOI: 10.1038/s41556-017-0011-1
Nature Cell Biology 20/1 2020-02-12
2018 Ying Wai Chan, Stephen C. West
GEN1 endonuclease: Purification and nuclease assays
published pages: 527-542, ISSN: , DOI: 10.1016/bs.mie.2017.11.020
Methods in Enzymology 600 2020-02-12
2017 Shah Punatar, R. Martin, M. J. Wyatt, H. D. Chan, Y. W. West, S. C.
Resolution of single and double Holliday junction recombination intermediates by GEN1
published pages: 443-450, ISSN: 0027-8424, DOI: 10.1073/pnas.1619790114
Proc Natl Acad Sci U S A 114 2020-02-12
2018 Stephen C. West, Ying Wai Chan
Genome Instability as a Consequence of Defects in the Resolution of Recombination Intermediates
published pages: 34256, ISSN: 0091-7451, DOI: 10.1101/sqb.2017.82.034256
Cold Spring Harbor Symposia on Quantitative Biology 82 2020-02-12
2015 Stephen C. West, Miguel G. Blanco, Ying Wai Chan, Joao Matos, Shriparna Sarbajna, Haley D.M. Wyatt
Resolution of Recombination Intermediates: Mechanisms and Regulation
published pages: 103-109, ISSN: 0091-7451, DOI: 10.1101/sqb.2015.80.027649
Cold Spring Harbor Symposia on Quantitative Biology 80 2020-02-12
2017 Joao Matos, Stephen C. West
Analysis of Structure-Selective Endonuclease Activities From Yeast and Human Extracts
published pages: 271-286, ISSN: , DOI: 10.1016/bs.mie.2017.03.005
Methods in Enzymology 591 2020-02-12
2018 Rajvee Shah Punatar, Stephen C. West
Preparation and resolution of Holliday junction DNA recombination intermediates
published pages: 569-590, ISSN: , DOI: 10.1016/bs.mie.2017.11.022
Methods in Enzymology 600 2020-02-12
2017 Haley D.M. Wyatt, Rob C. Laister, Stephen R. Martin, Cheryl H. Arrowsmith, Stephen C. West
The SMX DNA Repair Tri-nuclease
published pages: 848-860.e11, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2017.01.031
Molecular Cell 65/5 2020-02-12
2017 Haley D.M. Wyatt, Stephen C. West
SMX makes the cut in genome stability
published pages: , ISSN: 1949-2553, DOI: 10.18632/oncotarget.22420
Oncotarget 8/61 2020-02-12
2018 Ying Wai Chan, Stephen C. West
A new class of ultrafine anaphase bridges generated by homologous recombination
published pages: 1-9, ISSN: 1538-4101, DOI: 10.1080/15384101.2018.1515555
Cell Cycle 2020-02-12

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