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Nature 455, 633-637 (2 October 2008) | doi:10.1038/nature07283; Received 3 June 2008; Accepted 23 July 2008; Published online 31 August 2008

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Structure of the Tribolium castaneum telomerase catalytic subunit TERT

Andrew J. Gillis1, Anthony P. Schuller1 & Emmanuel Skordalakes1

  1. Gene Expression and Regulation Program, The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA

Correspondence to: Emmanuel Skordalakes1 Correspondence and requests for materials should be addressed to E.S. (Email: skorda@wistar.org).

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A common hallmark of human cancers is the overexpression of telomerase, a ribonucleoprotein complex that is responsible for maintaining the length and integrity of chromosome ends. Telomere length deregulation and telomerase activation is an early, and perhaps necessary, step in cancer cell evolution. Here we present the high-resolution structure of the Tribolium castaneum catalytic subunit of telomerase, TERT. The protein consists of three highly conserved domains, organized into a ring-like structure that shares common features with retroviral reverse transcriptases, viral RNA polymerases and B-family DNA polymerases. Domain organization places motifs implicated in substrate binding and catalysis in the interior of the ring, which can accommodate seven to eight bases of double-stranded nucleic acid. Modelling of an RNA–DNA heteroduplex in the interior of this ring demonstrates a perfect fit between the protein and the nucleic acid substrate, and positions the 3'-end of the DNA primer at the active site of the enzyme, providing evidence for the formation of an active telomerase elongation complex.

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