Evidence map›Paper›PMID 35501303›Full record

ArticleNature communications2022

Mre11-Rad50 oligomerization promotes DNA double-strand break repair.

Vera M Kissling, Giordano Reginato, Eliana Bianco, Kristina Kasaciunaite, Janny Tilma, Gea Cereghetti, Natalie Schindler, Sung Sik Lee, Raphaël Guérois, Brian Luke and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Non-coding RNA · 2025
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Dynamic Properties of the DNA Damage Response Mre11/Rad50 Complex.International journal of molecular sciences · 2023
    Review
  18. Article
  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

13 authors.

Vera M KisslingDepartment of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland.ORCID 0000-0002-4524-9905
Giordano Reginato *Department of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland.
Eliana Bianco *Department of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland.ORCID 0000-0003-1418-0527
Kristina KasaciunaitePeter Debye Institute for Soft Matter Physics, Universität Leipzig, 04103, Leipzig, Germany.
Janny TilmaDepartment of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland.
Gea CereghettiDepartment of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland.ORCID 0000-0001-7732-9435
Natalie SchindlerInstitute for Developmental and Neurobiology (IDN), Johannes Gutenberg University, 55128, Mainz, Germany.
Sung Sik LeeDepartment of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland.
Raphaël GuéroisInstitute for Integrative Biology of the Cell (I2BC), Commissariat à l'Energie Atomique, CNRS, Université Paris-Sud, Université Paris-Saclay, 91190, Gif-sur-Yvette, France.ORCID 0000-0001-5294-2858
Brian LukeInstitute for Developmental and Neurobiology (IDN), Johannes Gutenberg University, 55128, Mainz, Germany.
Ralf SeidelPeter Debye Institute for Soft Matter Physics, Universität Leipzig, 04103, Leipzig, Germany.ORCID 0000-0002-6642-053X
Petr CejkaDepartment of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland. petr.cejka@irb.usi.ch.
Matthias PeterDepartment of Biology, Institute of Biochemistry, Eidgenössische Technische Hochschule (ETH), 8093, Zürich, Switzerland. matthias.peter@bc.biol.ethz.ch.ORCID 0000-0002-2160-6824

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The conserved Mre11-Rad50 complex is crucial for the detection, signaling, end tethering and processing of DNA double-strand breaks. While it is known that Mre11-Rad50 foci formation at DNA lesions accompanies repair, the underlying molecular assembly mechanisms and functional implications remained unclear. Combining pathway reconstitution in electron microscopy, biochemical assays and genetic studies, we show that S. cerevisiae Mre11-Rad50 with or without Xrs2 forms higher-order assemblies in solution and on DNA. Rad50 mediates such oligomerization, and mutations in a conserved Rad50 beta-sheet enhance or disrupt oligomerization. We demonstrate that Mre11-Rad50-Xrs2 oligomerization facilitates foci formation, DNA damage signaling, repair, and telomere maintenance in vivo. Mre11-Rad50 oligomerization does not affect its exonuclease activity but drives endonucleolytic cleavage at multiple sites on the 5'-DNA strand near double-strand breaks. Interestingly, mutations in the human RAD50 beta-sheet are linked to hereditary cancer predisposition and our findings might provide insights into their potential role in chemoresistance.

Indexed as

Saccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAcid Anhydride HydrolasesDNADNA-Binding ProteinsEndodeoxyribonucleasesExodeoxyribonucleasesHumansAcid Anhydride HydrolasesDNADNA-Binding ProteinsEndodeoxyribonucleasesExodeoxyribonucleasesMRE11 protein, S cerevisiaeRAD50 protein, humanRAD50 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID35501303
PMCPMC9061753

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.