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dc.contributor.authorShivji, MKKen
dc.contributor.authorDavies, Owenen
dc.contributor.authorSavill, JMen
dc.contributor.authorBates, DLen
dc.contributor.authorPellegrini, Lucaen
dc.contributor.authorVenkitaraman, Ashoken
dc.date.accessioned2017-04-11T13:59:18Z
dc.date.available2017-04-11T13:59:18Z
dc.date.issued2006-08-16en
dc.identifier.issn0305-1048
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263595
dc.description.abstractHuman BRCA2, a breast and ovarian cancer suppressor, binds to the DNA recombinase RAD51 through eight conserved BRC repeats, motifs of similar to 30 residues, dispersed across a large region of the protein. BRCA2 is essential for homologous recombination in vivo, but isolated BRC repeat peptides can prevent the assembly of RAD51 into active nucleoprotein filaments in vitro, suggesting a model in which BRCA2 sequesters RAD51 in undamaged cells, and promotes recombinase function after DNA damage. How BRCA2 might fulfill these dual functions is unclear. We have purified a fragment of human BRCA2 (BRCA2(BRC1-8)) with 1127 residues spanning all 8 BRC repeats but excluding the C-terminal DNA-binding domain (BRCA2(CTD)). BRCA2(BRC1-8) binds RAD51 nucleoprotein filaments in a ternary complex, indicating it may organize RAD51 on DNA. Human RAD51 is relatively ineffective in vitro at strand exchange between homologous DNA molecules unless non-physiological ions like NH+4 are present. In an ionic milieu more typical of the mammalian nucleus, BRCA2(BRC1-8) stimulates RAD51-mediated strand exchange, suggesting it may be an essential co-factor in vivo. Thus, the human BRC repeats, embedded within their surronding sequences as an eight-repeat unit, mediate homologous recombination independent of the BRCA2(CTD) through a previously unrecognized role in control of RAD51 activity.
dc.description.sponsorshipThis work was supported by a Senior Non-Clinical Fellowship to L.P. from the Wellcome Trust and a BBSRC PhD studentship to O.R.D., and in ARV's laboratory by the Medical Research Council and a Cancer Research UK PhD studentship to D.L.B. Funding to pay the Open Access publication charges for this article was provided by the Medical Research Council.
dc.language.isoenen
dc.publisherOxford University Press
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectDNA-repairen
dc.subjectstabilityen
dc.subjectSEQUENCEen
dc.subjectINSIGHTSen
dc.subjectreplicationen
dc.subjecthomologous recombinationen
dc.subjectFILAMENTen
dc.subjectCANCER SUSCEPTIBILITY GENEen
dc.subjectHUMAN RAD51 PROTEINen
dc.subjectPOLARITYen
dc.titleA region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchangeen
dc.typeArticle
prism.endingPage4011
prism.issueIdentifier14en
prism.publicationDate2006en
prism.publicationNameNucleic Acids Researchen
prism.startingPage4000
prism.volume34en
dc.identifier.doi10.17863/CAM.8947
dcterms.dateAccepted2006-07-03en
rioxxterms.versionofrecord10.1093/nar/gkl505en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/en
rioxxterms.licenseref.startdate2006-08-16en
dc.contributor.orcidPellegrini, Luca [0000-0002-9300-497X]
dc.identifier.eissn1362-4962
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G0600332)
pubs.funder-project-idWellcome Trust (071102/Z/03/Z)
pubs.funder-project-idMRC (G9900064)
pubs.funder-project-idMRC (G0700651)


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International