ArticleProceedings of the National Academy of Sciences of the United States of America2014
A self-regulating template in human telomerase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- RTEL1 mutation modifies dyskeratosis congenita caused by a telomerase RNA template mutation.Nature communications · 2026Article
- Development of a microarray based telomerase binding assay reveals unusual binding of a cytochalasin derivative.Scientific reports · 2025Article
- A persistent variant telomere sequence in a human pedigree.Nature communications · 2024Article
- Orchestrating nucleic acid-protein interactions at chromosome ends: telomerase mechanisms come into focus.Nature structural & molecular biology · 2023Review
- Telomerase structural biology comes of age.Current opinion in structural biology · 2022Review
- Hydrosoluble Perylene Monoimide-Based Telomerase Inhibitors with Diminished Cytotoxicity.ACS omega · 2022Article
- Zipper head mechanism of telomere synthesis by human telomerase.Cell research · 2021Article
- Article
- Mechanisms of template handling and pseudoknot folding in human telomerase and their manipulation to expand the sequence repertoire of processive repeat synthesis.Nucleic acids research · 2018Article
- A single nucleotide incorporation step limits human telomerase repeat addition activity.The EMBO journal · 2018Article
- Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites.International journal of molecular sciences · 2018Review
- DNA-binding determinants and cellular thresholds for human telomerase repeat addition processivity.The EMBO journal · 2017Article
- Telomerase Mechanism of Telomere Synthesis.Annual review of biochemistry · 2017Review
- Progress in Human and Tetrahymena Telomerase Structure Determination.Annual review of biophysics · 2017Review
- Structural conservation in the template/pseudoknot domain of vertebrate telomerase RNA from teleost fish to human.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Evolutionary perspectives of telomerase RNA structure and function.RNA biology · 2016Review
- Physical Connectivity Mapping by Circular Permutation of Human Telomerase RNA Reveals New Regions Critical for Activity and Processivity.Molecular and cellular biology · 2016Article
- Human telomerase reverse transcriptase binds to a pre-organized hTR in vivo exposing its template.Nucleic acids research · 2016Article
- Structural basis of template-boundary definition in Tetrahymena telomerase.Nature structural & molecular biology · 2015Article
- A DNA-hairpin model for repeat-addition processivity in telomere synthesis.Nature structural & molecular biology · 2015Article
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6 authors.
Funding
Abstract
Telomerase is a specialized reverse transcriptase (RT) containing an intrinsic telomerase RNA (TR) component. It synthesizes telomeric DNA repeats, (GGTTAG)n in humans, by reiteratively copying a precisely defined, short template sequence from the integral TR. The specific mechanism of how the telomerase active site uses this short template region accurately and efficiently during processive DNA repeat synthesis has remained elusive. Here we report that the human TR template, in addition to specifying the DNA sequence, is embedded with a single-nucleotide signal to pause DNA synthesis. After the addition of a dT residue to the DNA primer, which is specified by the 49 rA residue in the template, telomerase extends the DNA primer with three additional nucleotides and then pauses DNA synthesis. This sequence-defined pause site coincides precisely with the helix paired region 1 (P1)-defined physical template boundary and precludes the incorporation of nontelomeric nucleotides from residues outside the template region. Furthermore, this sequence-defined pausing mechanism is a key determinant, in addition to the P1-defined template boundary, for generating the characteristic 6-nt ladder banding pattern of telomeric DNA products in vitro. In the absence of the pausing signal, telomerase stalls nucleotide addition at multiple sites along the template, generating DNA products with heterogeneous terminal repeat registers. Our findings demonstrate that this unique self-regulating mechanism of the human TR template is essential for high-fidelity synthesis of DNA repeats.
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