Abstract
Telomeres, the specialized DNA-protein complexes found at the termini of all linear eukaryotic chromosomes, protect chromosomes from degradation and end-to-end fusion. The protection of telomeres 1 (POT1) protein binds the single-stranded overhang at the ends of chromosomes in diverse eukaryotes. It is essential for chromosome end-protection and involved in telomere length regulation. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Through structural and biochemical studies, we have demonstrated that human TPP1 is the missing human homolog of the β subunit of protozoan telomere end-binding-protein-complex (TEBPα-TEBPβ). Therefore, capping of telomeres by a TEBPα-TEBPβ/POT1-TPP1 dimer is more evolutionarily conserved than that had been expected. In addition, we also discovered that the human POT1-TPP1 complex is a processivity factor for telomerase.
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Acknowledgments
The authors thank N. F. Lue (Weill Medical College of Cornell University) for the His-SUMO protein expression vector, Z. Songyang (Baylor College of Medicine) and T. de Lange (The Rockefeller University) for TPP1 cDNA, J. L. Chen (Arizona State University), and C. W. Greider (The Johns Hopkins University School of Medicine) for the human TERT and TER plasmids. We also would like to thank T. C. Cech, E. R. Podell, and A. J. Zaug for the development of the human telomerase activity assay. M.L. is a Howard Hughes Medical Institute Early Career Scientist. This work was supported by an NIH grant (GM 083015-01 to M.L.), an American Cancer Society Research Scholar Award (to M.L.), and a Sidney Kimmel Scholar Award (to M.L.).
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Wang, F., Lei, M. (2011). Human Telomere POT1-TPP1 Complex and Its Role in Telomerase Activity Regulation. In: Songyang, Z. (eds) Telomeres and Telomerase. Methods in Molecular Biology, vol 735. Humana Press. https://doi.org/10.1007/978-1-61779-092-8_17
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DOI: https://doi.org/10.1007/978-1-61779-092-8_17
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