Evidence map›Paper›PMID 32755577›Full record

ArticleCell reports2020

Tousled-Like Kinases Suppress Innate Immune Signaling Triggered by Alternative Lengthening of Telomeres.

Sandra Segura-Bayona, Marina Villamor-Payà, Camille Stephan-Otto Attolini, Lars M Koenig, Maria Sanchiz-Calvo, Simon J Boulton, Travis H Stracker

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Article
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  9. Translational cancer research · 2024
    Article
  10. iScience · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Untousling the Role of Tousled-like Kinase 1 in DNA Damage Repair.International journal of molecular sciences · 2023
    Review
  19. Review
  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 3 institutions in 3 countries.

Sandra Segura-BayonaInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: sandra.segura-bayona@crick.ac.uk.
Marina Villamor-PayàInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
Camille Stephan-Otto AttoliniInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
Lars M KoenigDivision of Clinical Pharmacology, University Hospital, LMU Munich, 80337 Munich, Germany.
Maria Sanchiz-CalvoInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain.
Simon J BoultonThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Travis H StrackerInstitute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain. Electronic address: travis.stracker@nih.gov.
Institute for Research in Biomedicine · ESThe Francis Crick Institute · GBLMU Klinikum · DE

Funding

Cancer Research UK FC0010048Medical Research Council FC0010048Wellcome TrustWellcome Trust FC0010048
6 · The paper itself

Abstract

The Tousled-like kinases 1 and 2 (TLK1/2) control histone deposition through the ASF1 histone chaperone and influence cell cycle progression and genome maintenance, yet the mechanisms underlying TLK-mediated genome stability remain uncertain. Here, we show that TLK loss results in severe chromatin decompaction and altered genome accessibility, particularly affecting heterochromatic regions. Failure to maintain heterochromatin increases spurious transcription of repetitive elements and induces features of alternative lengthening of telomeres (ALT). TLK depletion culminates in a cGAS-STING-TBK1-mediated innate immune response that is independent of replication-stress signaling and attenuated by the depletion of factors required to produce extra-telomeric DNA. Analysis of human cancers reveals that chromosomal instability correlates with high TLK2 and low STING levels in many cohorts. Based on these findings, we propose that high TLK levels contribute to immune evasion in chromosomally unstable and ALT+ cancers.

Indexed as

Immunity, InnateSignal TransductionTelomere HomeostasisCell Line, TumorCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseHeterochromatinHumansMembrane ProteinsNeoplasmsNucleotidyltransferasesProtein KinasesProtein Serine-Threonine KinasesRecombination, GeneticSTING ProteinTelomerecGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseHeterochromatinMembrane ProteinsNucleotidyltransferasesProtein Kinasesprotein kinase UProtein Serine-Threonine KinasesSTING1 protein, humanSTING ProteinTBK1 protein, humanTLK1 protein, humanALTASF1cGAS-STINGH3.3heterochromatininnate immunityrepetitive elementstelomeresTLK1TLK2

Identifiers

PMID32755577
PMCPMC7408502
OpenAlexW3047016359

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.