53BP1-dependent NHEJ is crucial in the immune system, where it is necessary for immunoglobulin class switch recombination (CSR) and T cell receptor rearrangements (Difilippantonio et al., 2008, Manis et al., 2004, Ward et al., 2004), but this same process is oncogenic in cancers driven by BRCA1 mutation or loss (Bouwman et al., 2010, Bunting et al., 2010). The gene discussed is TP53BP1; the disease is cancer.