A damage independent role for 53BP1 that impacts break order and Igh architecture during CSR

ABSTRACT: During Class Switch Recombination (CSR) B cells replace the Igh Cμ/δ exons with another downstream constant region exon (CH), altering the antibody isotype. CSR occurs through the introduction of AID-mediated double strand break (DSBs) in switch regions and subsequent ligation of broken ends. Here we developed an assay to investigate the dynamics of DSB introduction in individual cells. We demonstrate that the upstream switch region Sμ is always targeted first 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 mediat

ORGANISM(S): Mus musculus

SUBMITTER: Jane Skok 

PROVIDER: E-GEOD-81180 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress