Evidence map›Paper›PMID 31685617›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

POT1-TPP1 differentially regulates telomerase via POT1 His266 and as a function of single-stranded telomere DNA length.

Mengyuan Xu, Janna Kiselar, Tawna L Whited, Wilnelly Hernandez-Sanchez, Derek J Taylor

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Telomere maintenance in African trypanosomes.Frontiers in molecular biosciences · 2023
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. USP7 Is a Master Regulator of Genome Stability.Frontiers in cell and developmental biology · 2020
    Review
  18. POT1-TPP1 telomere length regulation and disease.Computational and structural biotechnology journal · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Mengyuan XuDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH 44106.
Janna KiselarCenter for Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, OH 44106.
Tawna L WhitedDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH 44106.
Wilnelly Hernandez-SanchezDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH 44106.
Derek J TaylorDepartment of Pharmacology, Case Western Reserve University, Cleveland, OH 44106; derek.taylor@case.edu.ORCID 0000-0001-9932-1856
Case Western Reserve University · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Case Center for Synchrotron BiosciencesP30EB009998 · NIBIB · CASE WESTERN RESERVE UNIVERSITY · PI CHANCE, MARK R · 2009 to 2018
$8.4M
Development of high-dose time-resolved x-ray footprinting technologies to enable the next level of structural analysis for challenging biological problemsR01GM126218 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI RALSTON, CORIE Y · 2018 to 2025
$3.4M
Structural and molecular determinants of protein phosphatase 2A in Alzheimer's DiseaseR01CA240993 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NARLA, GOUTHAM, TAYLOR, DEREK JAMES · 2019 to 2023
$3.4M
Molecular interactions and regulatory events of telomere proteinsR01GM133841 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI TAYLOR, DEREK JAMES · 2019 to 2022
$1.7M
NCI NIH HHS P30 CA091842NCI NIH HHS R01 CA240993NIBIB NIH HHS P30 EB009998NIGMS NIH HHS R01 GM126218NIGMS NIH HHS R01 GM133841
6 · The paper itself

Abstract

Telomeres cap the ends of linear chromosomes and terminate in a single-stranded DNA (ssDNA) overhang recognized by POT1-TPP1 heterodimers to help regulate telomere length homeostasis. Here hydroxyl radical footprinting coupled with mass spectrometry was employed to probe protein-protein interactions and conformational changes involved in the assembly of telomere ssDNA substrates of differing lengths bound by POT1-TPP1 heterodimers. Our data identified environmental changes surrounding residue histidine 266 of POT1 that were dependent on telomere ssDNA substrate length. We further determined that the chronic lymphocytic leukemia-associated H266L substitution significantly reduced POT1-TPP1 binding to short ssDNA substrates; however, it only moderately impaired the heterodimer binding to long ssDNA substrates containing multiple protein binding sites. Additionally, we identified a telomerase inhibitory role when several native POT1-TPP1 proteins coat physiologically relevant lengths of telomere ssDNA. This POT1-TPP1 complex-mediated inhibition of telomerase is abrogated in the context of the POT1 H266L mutation, which leads to telomere overextension in a malignant cellular environment.

Indexed as

Mutation, MissensePoint MutationPolymorphism, Single NucleotideAmino Acid SubstitutionCRISPR-Cas SystemsDNA, Single-StrandedHCT116 CellsHumansLeukemia, Lymphocytic, Chronic, B-CellProtein BindingRecombinant ProteinsShelterin ComplexTelomereTelomere-Binding ProteinsTelomere HomeostasisACD protein, humanDNA, Single-StrandedPOT1 protein, humanRecombinant ProteinsShelterin ComplexTelomere-Binding Proteinschronic lymphocytic leukemiafootprintinghydroxyl radicalshelterin

Identifiers

PMID31685617
PMCPMC6876245
OpenAlexW2984630066

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.