False moves for survival: error-prone DNA repair in adaptive immunity

Genetic stability and flexibility are major determinants of organismic integrity and evolution, respectively. An intricate DNA repair network protects the genome from multiple environmental challenges, but complex specialized processes may also allow enhanced mutability in critical situations. The interdependence and interference of these two systems is best exemplified in the adaptive immune system. Here, the coordinated reprogramming of DNA processing pathways allows the adaptation of the antibody response to specific infections, but in parallel increases the risk of malignant transformation of the affected B cells. The respective decisions in DNA repair pathway choice have now been linked to damage bypass processes occurring at stalled replication forks. Future research in this area may shed light on fundamental questions of both immunology and genetics, and provide translational concepts for improved cancer prognosis and therapy.