DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions

• DOI: 10.1073/pnas.1719988115
• Publication Date: 2018-01-08T20:37:24Z
• Authors: Rohit A. Panchaks...; Xuefei Zhang; Vipul Kumar; Zhou Du; Pei-Chi Wei; Jennifer Kao; Junchao Dong; Frederick W. Alt
• Keywords: 0301 basic medicine; Mice; 03 medical and health sciences; DNA End-Joining Repair; Animals; High-Throughput Nucleotide Sequencing; DNA Breaks, Double-Stranded; Immunoglobulin Class Switching; Translocation, Genetic; Cell Line

Significance B lymphocytes change the type of antibody they express to combat infections though a DNA breakage and joining process termed antibody class switch recombination (CSR). During CSR, DNA breaks are introduced into two specific regions of the antibody locus, and these two DNA breaks are joined to make the new form of the antibody gene. Like other genomic breaks, CSR DNA breaks activate a cellular DNA damage response pathway that helps ensure their proper repair. We now show that, when certain components of the DNA damage response pathway are inactivated, B-cell CSR junctions show different molecular signatures, indicating that they are repaired by a less-efficient alternative DNA repair pathway instead of the normal general cellular DNA break repair pathway.