| First Author | Kirkham CM | Year | 2019 |
| Journal | Mol Cell | Volume | 74 |
| Issue | 3 | Pages | 584-597.e9 |
| PubMed ID | 30905508 | Mgi Jnum | J:275106 |
| Mgi Id | MGI:6303542 | Doi | 10.1016/j.molcel.2019.02.025 |
| Citation | Kirkham CM, et al. (2019) Cut-and-Run: A Distinct Mechanism by which V(D)J Recombination Causes Genome Instability. Mol Cell 74(3):584-597.e9 |
| abstractText | 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. |
