Evidence map›Paper›PMID 25128433›Full record

ArticleGenes & development2014

Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation.

Alec N Sexton, Samuel G Regalado, Christine S Lai, Gregory J Cost, Colleen M O'Neil, Fyodor D Urnov, Philip D Gregory, Rudolf Jaenisch, Kathleen Collins, Dirk Hockemeyer

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 115 citations in OpenAlex.

  1. Article
  2. Fission yeast RPA-TERT-Tpz1bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Telomere maintenance in African trypanosomes.Frontiers in molecular biosciences · 2023
    Review
  12. Article
  13. Review
  14. Review
  15. The evolution of metazoan shelterin.Genes & development · 2021
    Article
  16. The structurally conserved TELR region on shelterin protein TPP1 is essential for telomerase processivity but not recruitment.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  17. Review
  18. Article
  19. Article
  20. Review

20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Alec N SextonDepartment of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA;
Samuel G RegaladoDepartment of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA;
Christine S LaiThe Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;
Gregory J CostSangamo BioSciences, Inc., Richmond, California 94804, USA.
Colleen M O'NeilSangamo BioSciences, Inc., Richmond, California 94804, USA.
Fyodor D UrnovSangamo BioSciences, Inc., Richmond, California 94804, USA.
Philip D GregorySangamo BioSciences, Inc., Richmond, California 94804, USA.
Rudolf JaenischThe Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA;
Kathleen CollinsDepartment of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA; hockemeyer@berkeley.edu kcollins@berkeley.edu.
Dirk HockemeyerDepartment of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA; hockemeyer@berkeley.edu kcollins@berkeley.edu.
Sangamo BioSciences (United States) · USUniversity of California, Berkeley · USWhitehead Institute for Biomedical Research · US

Funding

GENOMIC IMPRINTING AND THE CLONING OF MICER37CA084198 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2000 to 2008
$9.2M
Epigenetics, Stem Cells, and CancerR01CA087869 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2001 to 2010
$8.2M
In Vitro Reprogramming of Somatic Cells into Pluripotent ES-like CellsR37HD045022 · NICHD · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2009 to 2017
$7.5M
Nuclear Cloning and the Reprogramming of the GenomeR01HD045022 · NICHD · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF · 2003 to 2008
$4.7M
Molecular Mechanism of X-linked Dyskeratosis CongenitaR01HL079585 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI COLLINS, KATHLEEN · 2004 to 2017
$4.1M
Telomerase function in human tumor and stem cell biologyR01CA196884 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI HOCKEMEYER, DIRK · 2015 to 2019
$1.7M
Howard Hughes Medical InstituteNCI NIH HHS R01 CA087869NCI NIH HHS R01-CA087869NCI NIH HHS R01 CA196884NCI NIH HHS R37 CA084198NCI NIH HHS R37-CA084198NHLBI NIH HHS R01 HL079585NHLBI NIH HHS R01-HL079585NICHD NIH HHS R01 HD045022NICHD NIH HHS R01-HD045022NICHD NIH HHS R37 HD045022
6 · The paper itself

Abstract

Telomere length homeostasis is essential for the long-term survival of stem cells, and its set point determines the proliferative capacity of differentiated cell lineages by restricting the reservoir of telomeric repeats. Knockdown and overexpression studies in human tumor cells showed that the shelterin subunit TPP1 recruits telomerase to telomeres through a region termed the TEL patch. However, these studies do not resolve whether the TPP1 TEL patch is the only mechanism for telomerase recruitment and whether telomerase regulation studied in tumor cells is representative of nontransformed cells such as stem cells. Using genome engineering of human embryonic stem cells, which have physiological telomere length homeostasis, we establish that the TPP1 TEL patch is genetically essential for telomere elongation and thus long-term cell viability. Furthermore, genetic bypass, protein fusion, and intragenic complementation assays define two distinct additional mechanisms of TPP1 involvement in telomerase action at telomeres. We demonstrate that TPP1 provides an essential step of telomerase activation as well as feedback regulation of telomerase by telomere length, which is necessary to determine the appropriate telomere length set point in human embryonic stem cells. These studies reveal and resolve multiple TPP1 roles in telomere elongation and stem cell telomere length homeostasis.

Indexed as

Embryonic Stem CellsEnzyme ActivationETS Translocation Variant 6 ProteinGene Knockout TechniquesGenetic Complementation TestHumansProto-Oncogene Proteins c-etsRepressor ProteinsShelterin ComplexTelomeraseTelomereTelomere-Binding ProteinsTelomere HomeostasisACD protein, humanETS Translocation Variant 6 ProteinPOT1 protein, humanProto-Oncogene Proteins c-etsRepressor ProteinsShelterin ComplexTelomeraseTelomere-Binding ProteinsTERT protein, humanembryonic stem cellshuman genome engineeringshelterintelomerasetelomere maintenance

Identifiers

PMID25128433
PMCPMC4197946
OpenAlexW2167009086

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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Registered trials

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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.