Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair

The Ku heterodimer (Ku70 and Ku80 subunits) contributes to genomic integrit y through its ability to bind DNA double-strand breaks and facilitate repai r by the non-homologous end-joining pathway. The crystal structure of the h uman Ku heterodimer was determined both alone and bound to a 55-nucleotide DNA element at 2.7 and 2.5 Angstrom resolution, respectively. Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a prefor med ring that encircles duplex DNA. The binding site can cradle two full tu rns of DNA while encircling only the central 3-4 base pairs (bp). Ku makes no contacts with DNA bases and few with the sugar-phosphate backbone, but i t fits sterically to major and minor groove contours so as to position the DNA helix in a defined path through the protein ring. These features seem w ell designed to structurally support broken DNA ends and to bring the DNA h elix into phase across the junction during end processing and ligation.