KU IS A GENERAL INHIBITOR OF DNA-PROTEIN COMPLEX-FORMATION AND TRANSCRIPTION

Ku is a ubiquitous and abundant DNA binding protein. Recently, it has been shown that Ku plays a crucial role in double stranded-DNA (dsDNA) break repair such as occurs during the V(D)J recombination of Ig gene s. Ku has also been found to provide DNA binding activity to the catal ytic domain of DNA-PK which is known to phosphorylate several transcri ption factors, suggesting that Ku is a multifunctional protein that pa rticipates as a component of several functional DNA-protein complexes. Here, we examined the interaction of Ku with several DNA binding prot eins. Firstly, the DNA binding interaction between Ku and well-charact erized transcription factors (OTF-1, Sp-1, AP-1) was analysed by EMSA. Although sequence non-specific, Ku was strongly competitive with thes e sequence specific transcription factors on compatible DNA elements, displacing them because of its high affinity association with DNA ends . Secondly, to determine whether this competitive effect was functiona lly relevant, we tested Ku in an in vitro transcription system with th e adenovirus major late promoter. We found that Ku inhibited transcrip tion from linear, but not from circular template DNA. These results su ggest that Ku inhibits transcription when it is able to bind to templa te DNA and that the inhibition is the result of Ku displacing specific transcription factors from DNA. Copyright (C) 1996 Elsevier Science L td.