InterPro domain: IPR006165

Ku70 (also known as XRCC6) is a eukaryotic protein that is involved in the repair of DNA double-strand breaks by non-homologous end-joining [ 1 , 2 ]. Ku is a heterodimer of approximately 70kDa and 80kDa subunits [ 3 ]. Both these subunits have strong sequence similarity and it has been suggested that they may have evolved by gene duplication from a homodimeric ancestor in eukaryotes [ 4 ]. Homologues of the eukaryotic DNA-end-binding protein Ku were identified in several bacterial and one archaeal genome using iterative database searches; these prokaryotic Ku members are homodimers that have been predicted to be involved in the DNA repair system, which is mechanistically similar to eukaryotic non-homologous end joining [ 4 , 5 ] though they are not members of this family. Recent findings have implicated yeast Ku in telomeric structure maintenance in addition to non-homologous end-joining. Some of the phenotypes of Ku-knockout mice may indicate a similar role for Ku at mammalian telomeres [ 6 ].

Evolutionary notes: With the current available phyletic information it is difficult to determine the correct evolutionary trajectory of the Ku domain. It is possible that the core Ku domain was present in bacteria and archaea even before the presence of the eukaryotes. Eukaryotes might have vertically inherited the Ku core protein from a common ancestor shared with a certain archaeal lineage, or through horizontal transfer from bacteria. Alternatively, the core Ku domain could have evolved in the eukaryotic lineage and then horizontally transferred to the prokaryotes. Sequencing of additional archaeal genomes and those of early-branching eukaryotes may help resolve the evolutionary history of the Ku domain.

Structure notes: The eukaryotic Ku heterodimer is comprised of an alpha/beta N-terminal, a central beta-barrel domain and a helical C-terminal arm [ 7 ]. Structural analysis of the Ku70/80 heterodimer bound to DNA indicates that subunit contacts lead to the formation of a highly charged channel through which the DNA passes without making any contacts with the DNA bases [ 7 ].

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. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412, 607-14
4. 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
5. Identification of bacterial homologues of the Ku DNA repair proteins. FEBS Lett. 500, 186-8
6. Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells. Curr. Biol. 11, 1192-6