dc.contributor.author | Kirkham, CM | |
dc.contributor.author | Scott, JNF | |
dc.contributor.author | Wang, X | |
dc.contributor.author | Smith, AL | |
dc.contributor.author | Kupinski, AP | |
dc.contributor.author | Ford, AM | |
dc.contributor.author | Westhead, DR | |
dc.contributor.author | Stockley, PG | |
dc.contributor.author | Tuma, R | |
dc.contributor.author | Boyes, J | |
dc.date.accessioned | 2019-04-10T09:43:43Z | |
dc.date.issued | 2019-05-02 | |
dc.identifier.citation | Molecular cell, 2019, 74 (3), pp. 584 - 597.e9 | |
dc.identifier.issn | 1097-2765 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3171 | |
dc.identifier.eissn | 1097-4164 | |
dc.identifier.doi | 10.1016/j.molcel.2019.02.025 | |
dc.description.abstract | V(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. | |
dc.format | Print-Electronic | |
dc.format.extent | 584 - 597.e9 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | COS Cells | |
dc.subject | NIH 3T3 Cells | |
dc.subject | Chromosomes | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Translocation, Genetic | |
dc.subject | Genomic Instability | |
dc.subject | Recombinases | |
dc.subject | Homeodomain Proteins | |
dc.subject | DNA | |
dc.subject | Base Sequence | |
dc.subject | DNA Breaks, Double-Stranded | |
dc.subject | Precursor Cell Lymphoblastic Leukemia-Lymphoma | |
dc.subject | HEK293 Cells | |
dc.subject | V(D)J Recombination | |
dc.subject | Chlorocebus aethiops | |
dc.title | Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-02-14 | |
rioxxterms.versionofrecord | 10.1016/j.molcel.2019.02.025 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular cell | |
pubs.issue | 3 | |
pubs.notes | No embargo | |
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-status | Published | |
pubs.volume | 74 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Biology of Childhood Leukaemia | |
dc.contributor.icrauthor | Ford, Anthony | |