Ku acts in a unique way at the mammalian telomere to prevent end joining
- Hsin-Ling Hsu1,5,
- David Gilley1,5,
- Sanjeev A. Galande1,
- M. Prakash Hande2,
- Beth Allen3,
- Sahn-Ho Kim1,
- Gloria C. Li4,
- Judith Campisi1,
- Terumi Kohwi-Shigematsu1, and
- David J. Chen1,6
- 1Department of Cell and Molecular Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA; 2Center for Radiological Research, Columbia University, New York, New York 10032, USA; 3Life Sciences Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA; 4Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
Abstract
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.
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Footnotes
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↵5 These authors contributed equally to this work.
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↵6 Corresponding author.
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E-MAIL DJChen{at}LBL.gov; FAX (510) 486-6816.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.844000.
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- Received August 19, 2000.
- Accepted September 29, 2000.
- Cold Spring Harbor Laboratory Press
