Evidence map›Paper›PMID 29228254›Full record

ArticleNucleic acids research2018

Structural and functional analysis of an OB-fold in human Ctc1 implicated in telomere maintenance and bone marrow syndromes.

Prashanth K Shastrula, Cory T Rice, Zhuo Wang, Paul M Lieberman, Emmanuel Skordalakes

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
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  12. Structural biology of telomeres and telomerase.Cellular and molecular life sciences : CMLS · 2020
    Review
  13. POT1-TPP1 telomere length regulation and disease.Computational and structural biotechnology journal · 2020
    Review
  14. Roles of OB-Fold Proteins in Replication Stress.Frontiers in cell and developmental biology · 2020
    Review
  15. Review
  16. 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

5 authors at 1 institution in 1 country.

Prashanth K ShastrulaThe Wistar Institute, Gene expression and regulation program, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Cory T RiceThe Wistar Institute, Gene expression and regulation program, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Zhuo WangThe Wistar Institute, Gene expression and regulation program, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Paul M LiebermanThe Wistar Institute, Gene expression and regulation program, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Emmanuel SkordalakesThe Wistar Institute, Gene expression and regulation program, 3601 Spruce Street, Philadelphia, PA 19104, USA.
The Wistar Institute · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9M
Role of TERRA in Telomere Maintenance and Telomere Stress ResponseR01CA140652 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2010 to 2025
$6.0M
Targeting telomerase for melanoma therapeuticsR01CA201312 · NCI · WISTAR INSTITUTE · PI SKORDALAKES, EMMANUEL · 2016 to 2020
$2.4M
NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA140652NCI NIH HHS R01 CA201312
6 · The paper itself

Abstract

The human CST (Ctc1, Stn1 and Ten1) complex binds the telomeric overhang and regulates telomere length by promoting C-strand replication and inhibiting telomerase-dependent G-strand synthesis. Structural and biochemical studies on the human Stn1 and Ten1 complex revealed its mechanism of assembly and nucleic acid binding. However, little is known about the structural organization of the multi-domain Ctc1 protein and how each of these domains contribute to telomere length regulation. Here, we report the structure of a central domain of human Ctc1. The structure reveals a canonical OB-fold with the two identified disease mutations (R840W and V871M) contributing to the fold of the protein. In vitro assays suggest that although this domain is not contributing directly to Ctc1's substrate binding properties, it affects full-length Ctc1 localization to telomeres and Stn1-Ten1 binding. Moreover, functional assays show that deletion of the entire OB-fold domain leads to significant increase in telomere length, frequency of internal single G-strands and fragile telomeres. Our findings demonstrate that a previously unknown OB-fold domain contributes to efficient Ctc1 telomere localization and chromosome end maintenance.

Indexed as

Protein FoldingTelomere HomeostasisAmino Acid SequenceBone MarrowCrystallography, X-RayHEK293 CellsHumansModels, MolecularMutationProtein BindingProtein DomainsSequence Homology, Amino AcidSyndromeTelomereTelomere-Binding ProteinsCtc1 protein, humanTelomere-Binding Proteins

Identifiers

PMID29228254
PMCPMC5778599
OpenAlexW2771541687

What OpenQuestion holds

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LicenceCC BY-NC
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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.