| First Author | Rocha PP | Year | 2016 |
| Journal | Cell Rep | Volume | 16 |
| Issue | 1 | Pages | 48-55 |
| PubMed ID | 27320916 | Mgi Jnum | J:238371 |
| Mgi Id | MGI:5819170 | Doi | 10.1016/j.celrep.2016.05.073 |
| Citation | Rocha PP, et al. (2016) A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination. Cell Rep 16(1):48-55 |
| abstractText | During class switch recombination (CSR), B cells replace the Igh Cmu or delta exons with another downstream constant region exon (CH), altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs) in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Smu is first targeted during recombination and that the mechanism underlying this control relies on 53BP1. Surprisingly, regulation of break order occurs through residual binding of 53BP1 to chromatin before the introduction of damage and independent of its established role in DNA repair. Using chromosome conformation capture, we show that 53BP1 mediates changes in chromatin architecture that affect break order. Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR. |
