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BRCA2Interact

Structural and biochemical characterization of pre-recombination complexes

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 BRCA2Interact project word cloud

Explore the words cloud of the BRCA2Interact project. It provides you a very rough idea of what is the project "BRCA2Interact" about.

inclusion    insights    career    training    length    coordinate    complexes    rad51    world    mechanisms    substantially    strand    incidence    mechanism    forming    microscopic    additional    paralogs    interplay    therapeutic    invaluable    instability    recombinational    shown    pairing    paralog    visualisation    laboratory    hr    filaments    palb2    underlying    chaperone    forms    critical    tumour    microscopy    breast    recombinase    proteins    offers    extend    facilitates    recombination    anticipate    interacts    uncover    biochemical    defects    avoidance    central    brca2    damage    position    suppressors    family    suppressor    mediated    class    members    perfect    molecular    mutations    sites    structural    me    environment    intervention    platform    question    purified    launch    assembly    disposition    protein    dna    cancer    acting    independent    genome    disease    filament    biochemistry    repair    electron    full    function    nucleoprotein    answer    plays    host    homologous    linked    exchange   

Project "BRCA2Interact" 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 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2014
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2017-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 183˙454.00
2    CANCER RESEARCH UK LBG UK (LONDON) participant 0.00

Map

 Project objective

Homologous recombination (HR) is an essential DNA repair mechanism and defects in different HR factors are linked with disease and cancer pre-disposition. The RAD51 recombinase plays a central role in HR, forming nucleoprotein filaments at sites of DNA damage and promoting homologous pairing and DNA strand exchange. RAD51 filament formation is mediated by the BRCA2 tumour suppressor, mutations in which lead to a high incidence of developing breast cancer. BRCA2 interacts with other HR factors, such as PALB2 and members of the RAD51 paralog family. Many of these proteins also function as tumour suppressors. The host laboratory has purified full-length BRCA2 protein and shown that it facilitates RAD51-mediated HR by acting as a molecular chaperone for RAD51 filament formation. This offers a unique position to extend our understanding of pre-recombinational protein assembly by inclusion of additional critical HR factors, and answer the important question how PALB2 and the RAD51 paralogs coordinate their activities with BRCA2 to promote the assembly of RAD51 filaments. To achieve this, I propose to:

i) Characterize the biochemical and structural properties of RAD51 paralog complexes ii) Define the interplay between BRCA2, PALB2, and the RAD51 paralogs in forming pre-recombination complexes for RAD51 assembly, using biochemical approaches and electron microscopic visualisation.

Given the importance of HR and its role in tumour avoidance, I anticipate our results to provide significant new insights into the molecular mechanisms underlying genome instability. Also, they may uncover novel targets for therapeutic intervention for breast cancer. Together, the proposed research will not only substantially advance knowledge of DNA repair but will also provide me with invaluable training in biochemistry, electron microscopy and project management in a world-class research environment. As such, it forms the perfect platform from which to launch my independent research career.

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The information about "BRCA2INTERACT" are provided by the European Opendata Portal: CORDIS opendata.

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