Repair of DNA Double-Strand Breaks by the Non-homologous End Joining Pathway

DNA double strand breaks (DSBs) pose a serious threat to genome stability. In vertebrates, these breaks are predominantly repaired by non-homologous end joining (NHEJ), which pairs DNA ends in a multi-protein synaptic complex to promote their direct ligation. NHEJ is a highly versatile pathway that utilizes an array of processing enzymes to modify damaged DNA ends and enable their ligation. The mechanisms of end synapsis and end processing have important implications for genome stability. Rapid and stable synapsis is necessary to limit chromosome translocations that result from the mispairing of DNA ends. Furthermore, end processing must be tightly regulated to minimize mutations at the break site. Here we review our current mechanistic understanding of vertebrate NHEJ, with a particular focus on end synapsis and processing.