Holding it together: DNA end synapsis during non-homologous end joining

DNA double strand breaks (DSBs) are common lesions whose misrepair are drivers of oncogenic transformations. The non-homologous end joining (NHEJ) pathway repairs the majority of these breaks in vertebrates by directly ligating DNA ends back together. Upon formation of a DSB, a multiprotein complex is assembled on DNA ends which tethers them together within a synaptic complex. Synapsis is a critical step of the NHEJ pathway as loss of synapsis can result in mispairing of DNA ends and chromosome translocations. As DNA ends are commonly incompatible for ligation, the NHEJ machinery must also process ends to enable rejoining. This review describes how recent progress in single-molecule approaches and cryo-EM have advanced our molecular understanding of DNA end synapsis during NHEJ and how synapsis is coordinated with end processing to determine the fidelity of repair.

Automated summary

DNA double strand breaks (DSBs) are common lesions that can lead to cancer. The non-homologous end joining (NHEJ) pathway repairs the majority of these breaks by directly ligating DNA ends together. Recent advancements in single-molecule approaches and cryo-EM have improved our understanding of how DNA end synapsis and processing are coordinated in NHEJ, which is crucial for accurate repair.