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dc.contributor.authorKirkham, CMen_US
dc.contributor.authorScott, JNFen_US
dc.contributor.authorWang, Xen_US
dc.contributor.authorSmith, ALen_US
dc.contributor.authorKupinski, APen_US
dc.contributor.authorFord, AMen_US
dc.contributor.authorWesthead, DRen_US
dc.contributor.authorStockley, PGen_US
dc.contributor.authorTuma, Ren_US
dc.contributor.authorBoyes, Jen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-04-10T09:43:43Z
dc.date.issued2019-05-02en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30905508en_US
dc.identifierS1097-2765(19)30136-4en_US
dc.identifier.citationMol Cell, 2019, 74 (3), pp. 584 - 597.e9en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3171
dc.identifier.eissn1097-4164en_US
dc.identifier.doi10.1016/j.molcel.2019.02.025en_US
dc.description.abstractV(D)J recombination is essential to generate antigen receptor diversity but is also a potent cause of genome instability. Many chromosome alterations that result from aberrant V(D)J recombination involve breaks at single recombination signal sequences (RSSs). A long-standing question, however, is how such breaks occur. Here, we show that the genomic DNA that is excised during recombination, the excised signal circle (ESC), forms a complex with the recombinase proteins to efficiently catalyze breaks at single RSSs both in vitro and in vivo. Following cutting, the RSS is released while the ESC-recombinase complex remains intact to potentially trigger breaks at further RSSs. Consistent with this, chromosome breaks at RSSs increase markedly in the presence of the ESC. Notably, these breaks co-localize with those found in acute lymphoblastic leukemia patients and occur at key cancer driver genes. We have named this reaction "cut-and-run" and suggest that it could be a significant cause of lymphocyte genome instability.en_US
dc.format.extent584 - 597.e9en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectRAG proteinsen_US
dc.subjectV(D)J recombinationen_US
dc.subjectacute lymphoblastic leukemiaen_US
dc.subjectchromosome translocationsen_US
dc.subjectdouble strand breaksen_US
dc.subjectgenome instabilityen_US
dc.titleCut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-02-14en_US
rioxxterms.versionofrecord10.1016/j.molcel.2019.02.025en_US
rioxxterms.licenseref.startdate2019-05-02en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfMol Cellen_US
pubs.issue3en_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublisheden_US
pubs.volume74en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamBiology of Childhood Leukaemiaen_US
dc.contributor.icrauthorFord, Anthonyen_US


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