Evidence map›Paper›PMID 33704371›Full record

ArticleThe Journal of cell biology2021

FUS-dependent liquid-liquid phase separation is important for DNA repair initiation.

Brunno R Levone, Silvia C Lenzken, Marco Antonaci, Andreas Maiser, Alexander Rapp, Francesca Conte, Stefan Reber, Jonas Mechtersheimer, Antonella E Ronchi, Oliver Mühlemann and 4 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 2 pooled it
11.1field-weighted citation impact, top 1% 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

125 citing papers in PubMed, 2 syntheses or guidelines pooled it, 195 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. RSF1-Dependent PAR Turnover Promotes 53BP1 Liquid Condensate Formation at DNA Damage Sites.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

65 more citing papers are in PubMed but not listed here.

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 5 institutions in 4 countries.

Brunno R LevoneDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Silvia C LenzkenDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Marco AntonaciDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Andreas Maiser *Department of Biology II, Center for Integrated Protein Science Munich, Ludwig Maximilian University of Munich, Planegg-Martinsried, Germany.
Alexander Rapp *Department of Biology, Technical University of Darmstadt, Darmstadt, Germany.
Francesca ConteDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Stefan ReberUK Dementia Research Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Jonas MechtersheimerUK Dementia Research Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Antonella E RonchiDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
Oliver MühlemannDepartment of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.
Heinrich LeonhardtDepartment of Biology II, Center for Integrated Protein Science Munich, Ludwig Maximilian University of Munich, Planegg-Martinsried, Germany.
M Cristina CardosoDepartment of Biology, Technical University of Darmstadt, Darmstadt, Germany.
Marc-David RueppUK Dementia Research Institute, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Silvia M L BarabinoDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
University of Milano-Bicocca · ITKing's College London · GBCenter for Integrated Protein Science Munich · DETechnische Universität Darmstadt · DEUniversity of Bern · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA-binding proteins (RBPs) are emerging as important effectors of the cellular DNA damage response (DDR). The RBP FUS is implicated in RNA metabolism and DNA repair, and it undergoes reversible liquid-liquid phase separation (LLPS) in vitro. Here, we demonstrate that FUS-dependent LLPS is necessary for the initiation of the DDR. Using laser microirradiation in FUS-knockout cells, we show that FUS is required for the recruitment to DNA damage sites of the DDR factors KU80, NBS1, and 53BP1 and of SFPQ, another RBP implicated in the DDR. The relocation of KU80, NBS1, and SFPQ is similarly impaired by LLPS inhibitors, or LLPS-deficient FUS variants. We also show that LLPS is necessary for efficient γH2AX foci formation. Finally, using superresolution structured illumination microscopy, we demonstrate that the absence of FUS impairs the proper arrangement of γH2AX nanofoci into higher-order clusters. These findings demonstrate the early requirement for FUS-dependent LLPS in the activation of the DDR and the proper assembly of DSB repair complexes.

Indexed as

Cell LineCell Line, TumorDNA DamageDNA RepairHEK293 CellsHeLa CellsHumansProtein BindingProtein DomainsRNA-Binding Protein FUSRNA-Binding ProteinsFUS protein, humanRNA-Binding Protein FUSRNA-Binding Proteins

Identifiers

PMID33704371
PMCPMC7953258
OpenAlexW3133793763

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.