Evidence map›Paper›PMID 34718732›Full record

ArticleNucleic acids research2021

CST does not evict elongating telomerase but prevents initiation by ssDNA binding.

Arthur J Zaug, Ci Ji Lim, Conner L Olson, Maria T Carilli, Karen J Goodrich, Deborah S Wuttke, Thomas R Cech

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 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

23 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Telomere maintenance and the DNA damage response: a paradoxical alliance.Frontiers in cell and developmental biology · 2024
    Article
  11. Review
  12. POT1 recruits and regulates CST-Polα/Primase at human telomeres.bioRxiv : the preprint server for biology · 2023
    Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Telomere maintenance in African trypanosomes.Frontiers in molecular biosciences · 2023
    Review
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Arthur J ZaugDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
Ci Ji LimDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
Conner L OlsonDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
Maria T CarilliDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
Karen J GoodrichDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
Deborah S WuttkeDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.ORCID 0000-0002-8158-8795
Thomas R CechDepartment of Biochemistry, University of Colorado Boulder, Boulder, CO 80309, USA.
University of Colorado Boulder · USHoward Hughes Medical Institute · US

Funding

RPA and RPA-like Complexes at TelomeresR01GM139274 · NIGMS · UNIVERSITY OF COLORADO · PI WUTTKE, DEBORAH S. · 2020 to 2023
$1.2M
Structural understanding of human shelterin complex assembly at telomere and its regulation mechanism of telomerase activityR00GM131023 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI LIM, CI JI · 2020 to 2022
$730k
Howard Hughes Medical InstituteNIGMS NIH HHS R00 GM131023NIGMS NIH HHS R01 GM139274NIH HHS R00 GM131023
6 · The paper itself

Abstract

The CST complex (CTC1-STN1-TEN1) has been shown to inhibit telomerase extension of the G-strand of telomeres and facilitate the switch to C-strand synthesis by DNA polymerase alpha-primase (pol α-primase). Recently the structure of human CST was solved by cryo-EM, allowing the design of mutant proteins defective in telomeric ssDNA binding and prompting the reexamination of CST inhibition of telomerase. The previous proposal that human CST inhibits telomerase by sequestration of the DNA primer was tested with a series of DNA-binding mutants of CST and modeled by a competitive binding simulation. The DNA-binding mutants had substantially reduced ability to inhibit telomerase, as predicted from their reduced affinity for telomeric DNA. These results provide strong support for the previous primer sequestration model. We then tested whether addition of CST to an ongoing processive telomerase reaction would terminate DNA extension. Pulse-chase telomerase reactions with addition of either wild-type CST or DNA-binding mutants showed that CST has no detectable ability to terminate ongoing telomerase extension in vitro. The same lack of inhibition was observed with or without pol α-primase bound to CST. These results suggest how the switch from telomerase extension to C-strand synthesis may occur.

Indexed as

DNA Polymerase IDNA PrimaseDNA, Single-StrandedHEK293 CellsHumansMutationProtein BindingTelomeraseTelomere-Binding ProteinsCtc1 protein, humanDNA polymerase alpha-primaseDNA Polymerase IDNA PrimaseDNA, Single-StrandedStn1 protein, humanTelomeraseTelomere-Binding ProteinsTen1 protein, human

Identifiers

PMID34718732
PMCPMC8599947
OpenAlexW3211107810

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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.