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dc.contributor.authorDifilippantonio, Sen
dc.contributor.authorCeleste, Aen
dc.contributor.authorKruhlak, Men
dc.contributor.authorLee, Yen
dc.contributor.authorDifilippantonio, MJen
dc.contributor.authorFeigenbaum, Len
dc.contributor.authorJackson, Stephenen
dc.contributor.authorMcKinnon, PJen
dc.contributor.authorNussenzweig, Aen
dc.date.accessioned2019-02-13T12:11:55Z
dc.date.available2019-02-13T12:11:55Z
dc.date.issued2007en
dc.identifier.issn0022-1007
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/289369
dc.description.abstractThe chromosomal instability syndromes Nijmegen breakage syndrome (NBS) and ataxia telangiectasia (AT) share many overlapping phenotypes, including cancer predisposition, radiation sensitivity, cell-cycle checkpoint defects, immunodeficiency, and gonadal dysfunction. The NBS protein Nbs1 is not only a downstream target of AT mutated (ATM) kinase but also acts upstream, promoting optimal ATM activation, ATM recruitment to breaks, and ATM accessibility to substrates. By reconstituting Nbs1 knockout mice with bacterial artificial chromosomes, we have assessed the contribution of distinct regions of Nbs1 to the ATM-dependent DNA damage response. We fi nd that T cell and oocyte development, as well as DNA damage-induced G2/M and S phase checkpoint arrest and radiation survival are dependent on the N-terminal forkhead-associated domain, but not on the principal residues phosphorylated by ATM (S278 and S343) or on the evolutionarily conserved C-terminal region of Nbs1. However, the C-terminal region regulates irradiation-induced apoptosis. These studies provide insight into the complex interplay between Nbs1 and ATM in the DNA damage response.
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectdouble-strand breaksen
dc.subjectmre11 complexen
dc.subjectataxia-telangiectasiaen
dc.subjectionizing-radiationen
dc.subjects-phase checkpointen
dc.subjectatm activationen
dc.subjectDNA-damage-responseen
dc.subjectforkhead-associated domainen
dc.subjectmre11-rad50-nbs1 complexen
dc.subjectnijmegen-breakage-syndromeen
dc.titleDistinct domains in Nbs1 regulate irradiation-induced checkpoints and apoptosisen
dc.typeArticle
prism.endingPage1011
prism.issueIdentifier5en
prism.publicationDate2007en
prism.publicationNameJOURNAL OF EXPERIMENTAL MEDICINEen
prism.startingPage1003
prism.volume204en
dc.identifier.doi10.17863/CAM.36616
rioxxterms.versionofrecord10.1084/Jem.20070319en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2007en
dc.contributor.orcidJackson, Stephen [0000-0001-9317-7937]
dc.identifier.eissn0022-1007
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (A5290)


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