The biogenesis and regulation of telomerase holoenzymes
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TLDR
Insights that have been gained into the cellular pathways for biogenesis and regulation of telomerase ribonucleoproteins raise new questions, particularly concerning the dynamic nature of this unique polymerase.Abstract:
Chromosome stability requires a dynamic balance of DNA loss and gain in each terminal tract of telomeric repeats. Repeat addition by a specialized reverse transcriptase, telomerase, has an important role in maintaining this equilibrium. Insights that have been gained into the cellular pathways for biogenesis and regulation of telomerase ribonucleoproteins raise new questions, particularly concerning the dynamic nature of this unique polymerase.read more
Citations
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Journal ArticleDOI
Telomeres and Aging
TL;DR: The crucial role of telomeres in cell turnover and aging is highlighted by patients with 50% of normal telomere levels resulting from a mutation in one of the telomerase genes, implicated in a variety of disorders including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis, and cancer.
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Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs
TL;DR: The small nuclear and small nucleolar RNPs are two well studied classes of ncRNPs with elaborate assembly and trafficking pathways that provide paradigms for understanding the biogenesis of other nc RNPs.
Journal ArticleDOI
Targeting telomeres and telomerase
Anne De Cian,Laurent Lacroix,Laurent Lacroix,Céline Douarre,Nassima Temime-Smaali,Chantal Trentesaux,Jean-François Riou,Jean-Louis Mergny,Jean-Louis Mergny +8 more
TL;DR: The objective of this review is to present the latest view on the mechanism(s) of action of telomerase inhibitors, with an emphasis on a specific class of telomere ligands called G-quadruplex ligands, and to discuss their potential use in oncology.
Journal ArticleDOI
A Human Telomerase Holoenzyme Protein Required for Cajal Body Localization and Telomere Synthesis
Andrew S. Venteicher,Eladio Abreu,Zhaojing Meng,Kelly E. McCann,Rebecca M. Terns,Timothy D. Veenstra,Michael P. Terns,Steven E. Artandi +7 more
TL;DR: Depletion of TCAB1 by using RNA interference prevents TERC from associating with Cajal bodies, disrupts telomerase-telomere association, and abrogates telomere synthesis by telomersase.
Journal ArticleDOI
Identification of ATPases Pontin and Reptin as Telomerase Components Essential for Holoenzyme Assembly
TL;DR: The identification of the ATPases pontin and reptin as telomerase components through affinity purification of TERT from human cells reveals an unanticipated requirement for additional enzymes in telomersase biogenesis and suggests alternative approaches for inhibiting telomerases in cancer.
References
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Journal ArticleDOI
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
TL;DR: It is proposed that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes.
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Shelterin: the protein complex that shapes and safeguards human telomeres
TL;DR: The current data argue that shelterin is emerging as a protein complex with DNA remodeling activity that acts together with several associated DNA repair factors to change the structure of the telomeric DNA, thereby protecting chromosome ends.
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The RNA component of human telomerase
Junli Feng,Walter Funk,Sy Shi Wang,Scott L. Weinrich,Ariel A. Avilion,Choy-Pik Chiu,Robert Adams,Edwin Chang,Richard C. Allsopp,Jinghua Yu,Siyuan Le,Michael D. West,Calvin B. Harley,William H. Andrews,Carol W. Greider,Bryant Villeponteau +15 more
TL;DR: Human cell lines that expressed hTR mutated in the template region generated the predicted mutant telomerase activity, and cells transfected with an antisense hTR lost telomeric DNA and began to die after 23 to 26 doublings.
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A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.
Robert K. Moyzis,Judy M. Buckingham,L. S. Cram,M. Dani,Larry L. Deaven,M. D. Jones,J. Meyne,Robert L. Ratliff,Jung-Rung Wu +8 more
TL;DR: A highly conserved repetitive DNA sequence, (TTAGGG)n, has been isolated from a human recombinant repetitive DNA library and its similarity to functional telomeres isolated from lower eukaryotes suggest that this sequence is a functional human telomere.
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A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis.
TL;DR: The essential RNA component of this ribonucleoprotein enzyme has now been cloned and found to contain the sequence CAACCCCAA, which seems to be the template for the synthesis of TTGGGG repeats.