Crystal structure of human Ku bound to DNA. Ku70 is shown in purple, Ku80 in blue, and the DNA strand in green.

Both subunits of Ku have been knocked out in mouse. These mice exhibit chromosomal instability, indicating that NHEJ is important for genome maintenance.^[4][5]

In many organisms, Ku has additional functions at telomeres in addition to its role in DNA repair.^[6]

Unresolved double stranded breaks (DSB) in DNA lead to chromosomal abnormalities and associated pathologies, like cancer. Through the many years of evolution, cells have survived because of 2 main repair pathways. NHEJ involving Ku, DNApk, and DNA ligase 4 complex, repairs the DSB with high fidelity at the site of damage, without needing the matching sequence. The other is called homologous recombination (HR) because it does involve the use of the homologous sequence of DNA. The multifunctional protein complex that initiates HR is composed of Mre11-Rad50-Nbs1 (MRN) which detects DSB, and activates the ATM checkpoint kinase. Recently it was shown that maintaining Mre11 endonuclease activity is important cell survival but does not impair MRN's ability to recruit the necessary downstream factors to complete repair [7].

References

Reference 7: Cell, Vol 135, 97-109, 03 October 2008 Mre11 Dimers Coordinate DNA End Bridging and Nuclease Processing in Double-Strand-Break Repair R. Scott Williams,1,3,6 Gabriel Moncalian,1,3,6,8 Jessica S. Williams,1 Yoshiki Yamada,1 Oliver Limbo,1 David S. Shin,1,3 Lynda M. Groocock,1 Dana Cahill,4 Chiharu Hitomi,1,3 Grant Guenther,1 Davide Moiani,1,3 James P. Carney,4,7 Paul Russell,1,2,? and John A. Tainer1,3,5,??

Here is the abstract of the crystal structure of Ku heterodimer bound to DNA (ref. 2 link).

Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Walker JR, Corpina RA, Goldberg J. Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. The Ku heterodimer (Ku70 and Ku80 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 DNA 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.