dc.contributor.author | Mijušković, M | |
dc.contributor.author | Chou, Y-F | |
dc.contributor.author | Gigi, V | |
dc.contributor.author | Lindsay, CR | |
dc.contributor.author | Shestova, O | |
dc.contributor.author | Lewis, SM | |
dc.contributor.author | Roth, DB | |
dc.date.accessioned | 2018-06-13T08:16:37Z | |
dc.date.issued | 2015-09-01 | |
dc.identifier | http://www.sciencedirect.com/science/article/pii/S2211124715009195 | |
dc.identifier.citation | Cell Reports, 2015, 12 (11), pp. 1842 - 1852 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1846 | |
dc.description.abstract | Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification. | |
dc.format.extent | 1842 - 1852 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Elsevier BV | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | acute lymphoblastic-leukemia suppresses genomic instability mediated recombination notch1 gene in-vivo t-all activation mutations deletion jak1 Cell Biology | |
dc.title | Off-Target V(D)J Recombination Drives Lymphomagenesis and Is Escalated by Loss of the Rag2 C Terminus | |
dc.type | Journal Article | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2015-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell Reports | |
pubs.issue | 11 | |
pubs.notes | ISI Document Delivery No.: CR8PX Times Cited: 0 Cited Reference Count: 28 Mijuskovic, Martina Chou, Yi-Fan Gigi, Vered Lindsay, Cory R. Shestova, Olga Lewis, Susanna M. Roth, David B. Nih [ca-104588, pn1ey018244, 1r21ai097825-01] Funding: NIH grants CA-104588 and PN1EY018244 to D.B.R. and 1R21AI097825-01 to S.M.L. We thank Ellen Rothenberg (Caltech), and David Schatz (Yale University) for making alternatively formatted data available for analysis. SRA: SRP043567. 0 Cell press Cambridge | |
pubs.notes | Not known | |
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/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
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/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.volume | 12 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Mijuskovic, Martina | |