53BP1-mediated DNA double strand break repair: insert bad pun here.

53BP1 is an established player in the cellular response to DNA damage and is a canonical component of ionizing-radiation induced foci--that cadre of proteins which assemble at DNA double strand breaks following radiation exposure and which are readily visualized by immunofluorescence microscopy. While its roles in p53 regulation and cell cycle checkpoint activation have been studied for some time, the impact of 53BP1 on DNA double strand break rejoining has only come to light in the past few years. Convincing evidence now exists for 53BP1 significantly affecting the outcome of DNA double strand break repair in several contexts, many of which hint to an important role in modulating chromatin structure surrounding the break site. Here, we highlight the known and emerging roles of 53BP1 in DNA double strand break repair, including the repair of lesions induced within heterochromatin, following telomere uncapping, in long-range V(D)J recombination, during immunoglobulin class switch recombination and its much debated role in regulating resection during homologous recombination.