Evidence map›Paper›PMID 34883513›Full record

ArticleNucleic acids research2021

TIN2 is an architectural protein that facilitates TRF2-mediated trans- and cis-interactions on telomeric DNA.

Parminder Kaur, Ryan Barnes, Hai Pan, Ariana C Detwiler, Ming Liu, Chelsea Mahn, Jonathan Hall, Zach Messenger, Changjiang You, Jacob Piehler and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

12 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. TRF1 and TRF2: pioneering targets in telomere-based cancer therapy.Journal of cancer research and clinical oncology · 2024
    Review
  10. Review
  11. Review
  12. Article
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

14 authors at 3 institutions in 2 countries.

Parminder KaurPhysics Department, North Carolina State University, Raleigh, NC27695, USA.ORCID 0000-0001-9183-4315
Ryan BarnesDepartment of Environmental and Occupational Health, University of Pittsburgh, UPMC Hillman Cancer Center, PA 15213, USA.ORCID 0000-0003-0122-5773
Hai PanPhysics Department, North Carolina State University, Raleigh, NC27695, USA.
Ariana C DetwilerDepartment of Environmental and Occupational Health, University of Pittsburgh, UPMC Hillman Cancer Center, PA 15213, USA.ORCID 0000-0002-9311-5899
Ming LiuPhysics Department, North Carolina State University, Raleigh, NC27695, USA.
Chelsea MahnPhysics Department, North Carolina State University, Raleigh, NC27695, USA.
Jonathan HallCenter for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695, USA.ORCID 0000-0003-3191-0018
Zach MessengerToxicology Program, North Carolina State University, Raleigh, NC27695, USA.
Changjiang YouDepartment of Biology/Chemistry, Universität Osnabrück, Osnabrück 49076, Germany.ORCID 0000-0002-7839-6397
Jacob PiehlerDepartment of Biology/Chemistry, Universität Osnabrück, Osnabrück 49076, Germany.ORCID 0000-0002-2143-2270
Robert C SmartCenter for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695, USA.ORCID 0000-0002-6767-6756
Robert RiehnPhysics Department, North Carolina State University, Raleigh, NC27695, USA.ORCID 0000-0002-4408-3560
Patricia L OpreskoDepartment of Environmental and Occupational Health, University of Pittsburgh, UPMC Hillman Cancer Center, PA 15213, USA.ORCID 0000-0002-6470-2189
Hong WangPhysics Department, North Carolina State University, Raleigh, NC27695, USA.ORCID 0000-0003-0165-3559
North Carolina State University · USUPMC Hillman Cancer Center · USOsnabrück University · DE

Funding

Translational Research Support CoreP30ES025128 · NIEHS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI Sue Fenton · 2015 to 2026
$18.3M
Sequence and Structure Specific DNA Binding by Cohesin and Genome StabilityR01GM123246 · NIGMS · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI WANG, HONG · 2018 to 2021
$1.2M
NIEHS NIH HHS P30 ES025128NIGMS NIH HHS R01 GM123246
6 · The paper itself

Abstract

The telomere specific shelterin complex, which includes TRF1, TRF2, RAP1, TIN2, TPP1 and POT1, prevents spurious recognition of telomeres as double-strand DNA breaks and regulates telomerase and DNA repair activities at telomeres. TIN2 is a key component of the shelterin complex that directly interacts with TRF1, TRF2 and TPP1. In vivo, the large majority of TRF1 and TRF2 are in complex with TIN2 but without TPP1 and POT1. Since knockdown of TIN2 also removes TRF1 and TRF2 from telomeres, previous cell-based assays only provide information on downstream effects after the loss of TRF1/TRF2 and TIN2. Here, we investigated DNA structures promoted by TRF2-TIN2 using single-molecule imaging platforms, including tracking of compaction of long mouse telomeric DNA using fluorescence imaging, atomic force microscopy (AFM) imaging of protein-DNA structures, and monitoring of DNA-DNA and DNA-RNA bridging using the DNA tightrope assay. These techniques enabled us to uncover previously unknown unique activities of TIN2. TIN2S and TIN2L isoforms facilitate TRF2-mediated telomeric DNA compaction (cis-interactions), dsDNA-dsDNA, dsDNA-ssDNA and dsDNA-ssRNA bridging (trans-interactions). Furthermore, TIN2 facilitates TRF2-mediated T-loop formation. We propose a molecular model in which TIN2 functions as an architectural protein to promote TRF2-mediated trans and cis higher-order nucleic acid structures at telomeres.

Indexed as

AnimalsDNAHeLa CellsHumansMiceMice, Inbred C57BLMicroscopy, Atomic ForceNucleic Acid ConformationProtein BindingShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2DNAShelterin ComplexTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2Tinf2 protein, mouse

Identifiers

PMID34883513
PMCPMC8682769
OpenAlexW4200302607

What OpenQuestion holds

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LicenceCC BY-NC
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.