Abstract
Telomeres are DNA-protein structures that cap linear chromosomes and are essential for maintaining genomic stability and cell phenotype. We identified a novel human telomere-associated protein, TIN2, by interaction cloning using the telomeric DNA-binding-protein TRF1 as a bait. TIN2 interacted with TRF1 in vitro and in cells, and co-localized with TRF1 in nuclei and metaphase chromosomes. A mutant TIN2 that lacks amino-terminal sequences effects elongated human telomeres in a telomerase-dependent manner. Our findings suggest that TRF1 is insufficient for control of telomere length in human cells, and that TIN2 is an essential mediator of TRF1 function.
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Acknowledgements
We thank P. James for yeast PJ69-4A and sharing strains before publication; R. Weinberg for hTERT cDNA; and M. Bissell and R. Lupu for HMT-3522 and MDA-453 cells. Supported by research (AG09909) and training (AG00266) grants from the National Institute on Aging, a fellowship (2F1B-0026) from the University of California Breast Cancer Research Program and research grant from the Ellison Medical Foundation, under contract DE-AC03-76SF00098 from the U.S. Department of Energy.
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Kim, Sh., Kaminker, P. & Campisi, J. TIN2, a new regulator of telomere length in human cells. Nat Genet 23, 405–412 (1999). https://doi.org/10.1038/70508
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DOI: https://doi.org/10.1038/70508
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