NHEJ ͉ rAAV ͉ t-circles ͉ DNA-PK ͉ homologous recombination T he repair of DNA double-strand breaks (DSBs) is important for cellular survival, the maintenance of genomic integrity, and the prevention of tumorigenesis. DSBs can be caused by exposure to exogenous agents, including ionizing radiation and chemotherapeutic agents, and be generated by endogenous mechanisms, such as variable(diversity)joining [V(D)J] and class-switch recombination-processes required for the maturation of B and T lymphocytes. Moreover, the ends of linear chromosomes present cells with naturally occurring DSBs-i.e