PubMed Abstract
The ( and subunits) contributes to genomic integrity through its ability to bind DNA double-strand breaks and facilitate repair by the non-homologous end-joining pathway. The crystal structure of the human Ku heterodimer was determined both alone and bound to a 55-nucleotide element at 2.7 and 2.5 A resolution, respectively. Ku70 and Ku80 share a common topology and form a dyad-symmetrical molecule with a preformed ring that encircles duplex DNA. The binding site can cradle two full turns 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 it 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 well designed to structurally support broken DNA ends and to bring the DNA helix into phase across the junction during end processing and ligation. [1]
Ku Ring
The Ku ring is composed of a large base that cradles the DNA that consists of beta barrels in the heterodimer, and a narrow bridge that serves to protect the double strand break from base pairing with other DNA base pairs and prevents degradation. There is little interaction between the ring and the backbone or base pairs of DNA; instead, the ring associates with DNA by the large base fitting into the major grooves of the helix. The positive electrostatic charge caused by polarization of the ring also allows the negatively charged backbone of DNA to be guided into the correct position. The Ku protein also has a high affinity to DNA due to its form being preset for the helix. As a result of the asymmetric ring, there is a strong preference (Kd value of 1.5 to 4 X 10^-10 M) for the Ku ring to slide onto the ends of DNA. In addition, other asymmetric features prevent the Ku protein from sliding further on the DNA helix. While wrapping over the entire helix, the Ku ring is thin over the bridge, allowing ligases and polymerases to efficiently interact in DNA repair.
Domains
The beta barrels also serve as part of the cradle, fitting into the major groove of DNA over two turns.
