Multicomponent assemblies in DNA-double-strand break repair by NHEJ

Non-homologous end joining (NHEJ), a process for repair of DNA-breaks that does not require a DNA-template, involves synapsis, end-processing and ligation. Synapsis is initiated by assembly of the Ku-heterodimer on DNA broken ends, followed by the formation of DNA-dependent protein kinase (DNA-PK) - an assembly of the catalytic subunit (DNA-PKcs), the Ku-heterodimer and DNA. Recent progress in understanding the structural architecture of DNA-PK, achieved by X-ray crystallography and cryo-electron microscopy, has revealed a stage of DNA-PKcs on which other components from the pathway assemble and mediate kinase activity allosterically. This review provides a comparative overview of recently published structures of DNA-PK, together with a discussion of other complexes mediated by the Ku-heterodimer. It also shows that some binders are specific to particular patho-physiological conditions.