Structural basis for telomerase catalytic subunit tert binding to rna template and telomeric dna

ABSTRACT Telomerase is a specialized DNA polymerase that extends the 3′ ends of eukaryotic linear chromosomes, a process required for genomic stability and cell viability. Here we present

the crystal structure of the active _Tribolium castaneum_ telomerase catalytic subunit, TERT, bound to an RNA-DNA hairpin designed to resemble the putative RNA-templating region and

telomeric DNA. The RNA-DNA hybrid adopts a helical structure, docked in the interior cavity of the TERT ring. Contacts between the RNA template and motifs 2 and B′ position the

solvent-accessible RNA bases close to the enzyme active site for nucleotide binding and selectivity. Nucleic acid binding induces rigid TERT conformational changes to form a tight catalytic

complex. Overall, TERT–RNA template and TERT–telomeric DNA associations are remarkably similar to those observed for retroviral reverse transcriptases, suggesting common mechanistic aspects

of DNA replication between the two families of enzymes. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS ZIPPER HEAD MECHANISM OF TELOMERE SYNTHESIS BY HUMAN TELOMERASE Article Open

access 15 November 2021 STRUCTURES OF TELOMERASE AT SEVERAL STEPS OF TELOMERE REPEAT SYNTHESIS Article 12 May 2021 STRUCTURE OF ACTIVE HUMAN TELOMERASE WITH TELOMERE SHELTERIN PROTEIN TPP1

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ACKNOWLEDGEMENTS We would like to thank S.J. Gamblin and S. Pennell for helpful discussions. Funding for this project was generously provided by the Ellison Medical and the V Foundations as

well as the Pennsylvania Department of Health. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, USA

Meghan Mitchell, Andrew Gillis & Emmanuel Skordalakes * Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Japan Mizuko Futahashi 

& Haruhiko Fujiwara Authors * Meghan Mitchell View author publications You can also search for this author inPubMed Google Scholar * Andrew Gillis View author publications You can also

search for this author inPubMed Google Scholar * Mizuko Futahashi View author publications You can also search for this author inPubMed Google Scholar * Haruhiko Fujiwara View author

publications You can also search for this author inPubMed Google Scholar * Emmanuel Skordalakes View author publications You can also search for this author inPubMed Google Scholar

CONTRIBUTIONS E.S. designed the experiment plan, analyzed the data and wrote the manuscript; A.G. prepared the recombinant telomerase and carried out the reverse transcriptase assays; M.M.

carried out the TRAP assays; H.F. and M.F. provided advice with the _T. castaneum_ TRAP assays. CORRESPONDING AUTHOR Correspondence to Emmanuel Skordalakes. ETHICS DECLARATIONS COMPETING

INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–4 (PDF 2115 kb) RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Mitchell, M., Gillis, A., Futahashi, M. _et al._ Structural basis for telomerase catalytic subunit TERT binding to RNA template

and telomeric DNA. _Nat Struct Mol Biol_ 17, 513–518 (2010). https://doi.org/10.1038/nsmb.1777 Download citation * Received: 17 October 2009 * Accepted: 20 January 2010 * Published: 28 March

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