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 an large base that cradles the DNA, which is largely composed of the 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 degradation. As a result of the asymmetric ring, there is a strong preference (Kd = 1.5 to 4.0 X 10 for the Ku ring to slide onto the ends of DNA, with other asymmetric features preventing the Ku protein from sliding further on the DNA helix. The Ku ring, while wrapping over the entire helix, is thin over the bridge, allowing ligases and polymerases to efficiently interact in DNA repair. Instead of most DNA binding proteins, the Ku heterodimer contains a ring that encircles the DNA helix, with preference towards DNA ends. By binding to the DNA end, the Ku ring protects the broken DNA strands from degradation and from base pairing to another DNA strand.
Domains
The beta barrels also serve as part of the cradle, fitting into the major groove of DNA over two turns.
