Imperial College London
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ProfessorXiaodongZhang

Faculty of Medicine, Department of Infectious Disease

Professor of Macromolecular Structure and Function
 
 
 
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Contact

 

+44 (0)20 7594 3151xiaodong.zhang Website

 
 
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Assistant

 

Miss Kelly Butler +44 (0)20 7594 2763

 
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Location

 

104Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Shahid:2014:10.1038/nsmb.2899,
author = {Shahid, T and Soroka, J and Kong, EH and Malivert, L and McIlwraith, MJ and Pape, T and West, SC and Zhang, X},
doi = {10.1038/nsmb.2899},
journal = {Nature Structural and Molecular Biology},
pages = {962--968},
title = {Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor},
url = {http://dx.doi.org/10.1038/nsmb.2899},
volume = {21},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mutations in BRCA2 increase susceptibility to breast, ovarian and prostate cancers. The product of human BRCA2, BRCA2 protein, has a key role in the repair of DNA double-strand breaks and interstrand cross-links by RAD51-mediated homologous recombination. Here, we present a biochemical and structural characterization of full-length (3,418 amino acid) BRCA2, alone and in complex with RAD51. We show that BRCA2 facilitates nucleation of RAD51 filaments at multiple sites on single-stranded DNA. Three-dimensional EM reconstructions revealed that BRCA2 exists as a dimer and that two oppositely oriented sets of RAD51 molecules bind the dimer. Single-stranded DNA binds along the long axis of BRCA2, such that only one set of RAD51 monomers can form a productive complex with DNA and establish filament formation. Our data define the molecular mechanism by which this tumor suppressor facilitates RAD51-mediated homologous-recombinational repair.
AU  - Shahid,T
AU  - Soroka,J
AU  - Kong,EH
AU  - Malivert,L
AU  - McIlwraith,MJ
AU  - Pape,T
AU  - West,SC
AU  - Zhang,X
DO  - 10.1038/nsmb.2899
EP  - 968
PY  - 2014///
SN  - 1545-9985
SP  - 962
TI  - Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor
T2  - Nature Structural and Molecular Biology
UR  - http://dx.doi.org/10.1038/nsmb.2899
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000344513400005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/nsmb.2899
VL  - 21
ER  -
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