InterPro domain: IPR024193

This group consists of eukaryotic proteins containing the Ku80 domain. In eukaryotes it has been shown thatKu protein is involved in repairing DNA double-strand breaks by non-homologous end-joining [ 1 , 2 , 3 ]. Ku is a heterodimer of approximately 70kDa and 80kDa subunits [ 4 ]. Both these subunits have strong sequence similarity and ithas been suggested that they may have evolved by gene duplication from a homodimeric ancestor in eukaryotes[ 5 ]. The prokaryotic Ku members are homodimers and they have been predicted to beinvolved in the DNA repair system, which is mechanistically similar to the eukaryotic non-homologous end joining[ 5 , 6 ]. Recent findings have implicated yeast Ku in telomericstructure maintenance in addition to non-homologous end-joining [ 7 ]. Some of thephenotypes of Ku-knockout mice may indicate a similar role for Ku at mammalian telomeres [ 8 ].

Evolutionary notes: With the currently available phyletic information it is difficultto determine the correct evolutionary trajectory of the Ku domain. It is possible that the core Ku domain waspresent in bacteria and archaea even before the presence of the eukaryotes. Eukaryotes might have verticallyinherited the Ku-core protein from a common ancestor shared with a certain archaeal lineage or throughhorizontal transfer from bacteria. Alternatively, the core Ku domain could have evolved in the eukaryoticlineage and then horizontally transferred to the prokaryotes. Sequencing of additional archaeal genomes andthose of early-branching eukaryotes may help resolve the evolutionary history of the Ku domain.

Structurenotes: The eukaryotic Ku heterodimer is comprised of an alpha/beta N-terminal domain, a central beta-barreldomain and a helical C-terminal arm [ 9 ]. Structural analysis of the Ku70/80 heterodimerbound to DNA indicates that subunit contacts lead to the formation of a highly charged channel through which theDNA passes without making any contacts with the DNA bases [ 9 ].

For additionalinformation please see [ 9 ].

1. DNA double-strand break repair from head to tail. Curr. Opin. Struct. Biol. 12, 115-22
2. Ku, a DNA repair protein with multiple cellular functions? Mutat. Res. 434, 3-15
3. High G/C content of cohesive overhangs renders DNA end joining Ku-independent. DNA Repair (Amst.) 3, 13-21
4. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412, 607-14
5. Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system. Genome Res. 11, 1365-74
6. Identification of bacterial homologues of the Ku DNA repair proteins. FEBS Lett. 500, 186-8
7. Protection of telomeres by the Ku protein in fission yeast. Mol. Biol. Cell 11, 3265-75
8. Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells. Curr. Biol. 11, 1192-6
9. Characterization of the RNA binding properties of Ku protein. Biochemistry 37, 1336-43