ArticleThe EMBO journal2014
Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- Structures of nucleotide-bound human telomerase at several steps of its telomeric DNA repeat addition cycle.Nature communications · 2026Article
- Orchestrating nucleic acid-protein interactions at chromosome ends: telomerase mechanisms come into focus.Nature structural & molecular biology · 2023Review
- Interaction hub critical for telomerase recruitment and primer-template handling for catalysis.Life science alliance · 2023Article
- In vivo architecture of the telomerase RNA catalytic core in Trypanosoma brucei.Nucleic acids research · 2021Article
- Zipper head mechanism of telomere synthesis by human telomerase.Cell research · 2021Article
- Structural biology of human telomerase: progress and prospects.Biochemical Society transactions · 2021Review
- Review
- A structurally conserved human andProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structural biology of telomeres and telomerase.Cellular and molecular life sciences : CMLS · 2020Review
- Structural Biology of Telomerase.Cold Spring Harbor perspectives in biology · 2019Review
- Single-Molecule Analysis of Reverse Transcriptase Enzymes.Cold Spring Harbor perspectives in biology · 2019Review
- Telomerase structures and regulation: shedding light on the chromosome end.Current opinion in structural biology · 2019Review
- 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
- Article
- Direct observation of nucleic acid binding dynamics by the telomerase essential N-terminal domain.Nucleic acids research · 2018Article
- New perspectives on telomerase RNA structure and function.Wiley interdisciplinary reviews. RNA · 2018Review
- Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase.Nucleic acids research · 2018Article
- Structural biology of telomerase and its interaction at telomeres.Current opinion in structural biology · 2017Review
- 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
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
With eukaryotic genome replication, incomplete telomere synthesis results in chromosome shortening and eventual compromise of genome stability. Telomerase counteracts this terminal sequence loss by synthesizing telomeric repeats through repeated cycles of reverse transcription of its internal RNA template. Using human telomerase domain-complementation assays for telomerase reverse transcriptase protein (TERT) and RNA in combination with the first direct footprinting assay for telomerase association with bound DNA, we resolve mechanisms by which TERT domains and RNA motifs direct repeat synthesis. Surprisingly, we find that product-template hybrid is sensed in a length- and sequence-dependent manner to set the template 5' boundary. We demonstrate that the TERT N-terminal (TEN) domain determines active-site use of the atypically short primer-template hybrid necessary for telomeric-repeat synthesis. Also against expectation, we show that the remainder of TERT (the TERT ring) supports functional recognition and physical protection of single-stranded DNA adjacent to the template hybrid. These findings establish unprecedented polymerase recognition specificities for DNA-RNA hybrid and single-stranded DNA and suggest a new perspective on the mechanisms of telomerase specialization for telomeric-repeat synthesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.