Ku acts in a unique way at the mammalian telomere to prevent end joining

Telomeres are specialized DNA/protein structures that act as protective cap s to prevent end fusion events and to distinguish the chromosome ends from double-strand breaks. We report that TRF1 and Ku form a complex at the telo mere. The Ku and TRF1 complex is a specific high-affinity interaction, as d emonstrated by several in vitro methods, and exists in human cells as deter mined by coimmunoprecipitation experiments. Ku does not bind telomeric DNA directly but localizes to telomeric repeats via its interaction with TRF1. Primary mouse embryonic fibroblasts that are deficient for Ku80 accumulated a large percentage of telomere fusions, establishing that Ku plays a criti cal role in telomere capping in mammalian cells. We propose that Ku localiz es to internal regions of the telomere via a high-affinity interaction with TRF1. Therefore, Ku acts in a unique way at the telomere to prevent end jo ining.