In mammalian cells, the Ku and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) proteins are required for the correct acid efficient repair of DNA double-strand breaks. Ku comprises two tightly-associated subunits of ~69 and ~ 83 kDa, which are termed Ku70 and Ku80 (or Ku86), respectively. Previously, a number of regions of both Ku subunits have been demonstrated to be involved in their interaction, but the molecular mechanism of this interaction remains unknown. We have identified a region in Ku70 (amino acid residues 449-578) and a region in Ku80 (residues 439-592) that participate in Ku subunit interaction. Sequence analysis reveals that these interaction regions share sequence homology and suggests that the Ku subunits are structurally related. On binding to a DNA double-strand break, Ku is able to interact with DNA-PKcs, but how this interaction is mediated has not been defined. We show that the extreme C-terminus of Ku80, specifically the final 12 amino acid residues, mediates a highly specific interaction with DNA-PKcs. Strikingly, these residues appear to be conserved only in Ku80 sequences from vertebrate organisms. These data suggest that Ku has evolved to become part of the DNA-PK holoenzyme by acquisition of a protein-protein interaction motif at the C-terminus of Ku80.

Item Type:	Refereed Article
Research Division:	Biological Sciences
Research Group:	Biochemistry and cell biology
Research Field:	Enzymes
Objective Division:	Expanding Knowledge
Objective Group:	Expanding knowledge
Objective Field:	Expanding knowledge in the biological sciences
UTAS Author:	Gell, D (Dr David Gell)
ID Code:	64572
Year Published:	1999
Web of Science® Times Cited:	174
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2010-08-12
Last Modified:	2011-08-05
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