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Science 20 November 1998:
Vol. 282. no. 5393, pp. 1484 - 1487
DOI: 10.1126/science.282.5393.1484
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Reports

Tankyrase, a Poly(ADP-Ribose) Polymerase at Human Telomeres

Susan Smith, Izabela Giriat, Anja Schmitt, * Titia de Lange dagger

Tankyrase, a protein with homology to ankyrins and to the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP), was identified and localized to human telomeres. Tankyrase binds to the telomeric protein TRF1 (telomeric repeat binding factor-1), a negative regulator of telomere length maintenance. Like ankyrins, tankyrase contains 24 ankyrin repeats in a domain responsible for its interaction with TRF1. Recombinant tankyrase was found to have PARP activity in vitro, with both TRF1 and tankyrase functioning as acceptors for adenosine diphosphate (ADP)-ribosylation. ADP-ribosylation of TRF1 diminished its ability to bind to telomeric DNA in vitro, suggesting that telomere function in human cells is regulated by poly(ADP-ribosyl)ation.

The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
*   Present address: European Molecular Biology Laboratory-Heidelberg, Meyerhofstrasse 1, D-69117, Heidelberg, Germany.

dagger    To whom correspondence should be addressed. E-mail: delange{at}rockvax.rockefeller.edu

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Poly(ADP-ribose) Polymerase-2 (PARP-2) Is Required for Efficient Base Excision DNA Repair in Association with PARP-1 and XRCC1.
V. Schreiber, J.-C. Ame, P. Dolle, I. Schultz, B. Rinaldi, V. Fraulob, J. Menissier-de Murcia, and G. de Murcia (2002)
J. Biol. Chem. 277, 23028-23036
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RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA.
D. P. Morse, P. J. Aruscavage, and B. L. Bass (2002)
PNAS 99, 7906-7911
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Targeting Assay To Study the cis Functions of Human Telomeric Proteins: Evidence for Inhibition of Telomerase by TRF1 and for Activation of Telomere Degradation by TRF2.
K. Ancelin, M. Brunori, S. Bauwens, C.-E. Koering, C. Brun, M. Ricoul, J.-P. Pommier, L. Sabatier, and E. Gilson (2002)
Mol. Cell. Biol. 22, 3474-3487
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Regulators of Telomerase Activity.
L. J. Mauro and D. N. Foster (2002)
Am. J. Respir. Cell Mol. Biol. 26, 521-524
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A G-Quadruplex-Interactive Potent Small-Molecule Inhibitor of Telomerase Exhibiting in Vitro and in Vivo Antitumor Activity.
S. M. Gowan, J. R. Harrison, L. Patterson, M. Valenti, M. A. Read, S. Neidle, and L. R. Kelland (2002)
Mol. Pharmacol. 61, 1154-1162
   Abstract »    Full Text »    PDF »


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