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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.

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

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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