Abstract
During class switch recombination (CSR), B cells replace the Igh C mu 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 S mu 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.
Item Type: | Journal article |
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Faculties: | Medicine > Adolf Butenandt Institute |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-37755-3 |
ISSN: | 2211-1247 |
Language: | English |
Item ID: | 37755 |
Date Deposited: | 04. May 2017, 13:10 |
Last Modified: | 04. Nov 2020, 14:44 |