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Vol. 14, No. 22, pp. 2807-2812, November 15, 2000
1 Department of Cell and Molecular Biology, Life Sciences
Division, Lawrence Berkeley National Laboratory, Berkeley, California
94720, USA; 2 Center for Radiological Research, Columbia
University, New York, New York 10032, USA; 3 Life Sciences
Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA; 4 Department of Radiation Oncology, Memorial
Sloan-Kettering Cancer Center, New York, New York 10021, USA
Telomeres are specialized DNA/protein structures that act as
protective caps 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 telomere. The Ku and TRF1 complex is a specific
high-affinity interaction, as demonstrated by several in vitro methods,
and exists in human cells as determined 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 critical
role in telomere capping in mammalian cells. We propose that Ku
localizes 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 joining.
[Key Words: Telomere; TRF1; Ku]
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