Evidence map›Paper›PMID 40479710›Full record

ArticleNucleic acids research2025

Genome rearrangements induced by the stimulation of end-joining of DNA double strand breaks through multiple phosphorylation of MRE11 by the kinase PKB/AKT1.

Josée Guirouilh-Barbat, Iman Litchy Boueya, Camille Gelot, Gaëlle Pennarun, Christine Granotier-Beckers, Elodie Dardillac, Wei Yu, Chloé Lescale, Emilie Rass, Olivier Ariste and 9 more

Abstract read
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In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Josée Guirouilh-BarbatUniversité de Paris Cité, INSERM U1016, UMR 8104 CNRS, Institut Cochin, 24 rue du Faubourg St. Jacques, 75014 Paris, France.
Iman Litchy BoueyaUniversité de Paris Cité, INSERM U1016, UMR 8104 CNRS, Institut Cochin, 24 rue du Faubourg St. Jacques, 75014 Paris, France.
Camille GelotCNRS UMR 8200, Institut de Cancérologie Gustave-Roussy, Université Paris-Saclay, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
Gaëlle PennarunUniversité Paris-Saclay, INSERM, CEA, UMR Stabilité Génétique Cellules Souches et Radiations, F-92260 Fontenay-aux-Roses, France.ORCID 0000-0001-9881-9345
Christine Granotier-BeckersUniversité Paris-Saclay, INSERM, CEA, UMR Stabilité Génétique Cellules Souches et Radiations, F-92260 Fontenay-aux-Roses, France.ORCID 0000-0003-1063-1159
Elodie DardillacUniversité de Paris Cité, INSERM U1016, UMR 8104 CNRS, Institut Cochin, 24 rue du Faubourg St. Jacques, 75014 Paris, France.ORCID 0000-0002-2069-8309
Wei YuInstitut Pasteur, Université Paris Cité, INSERM U1223, Équipe Labellisée Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France.
Chloé LescaleInstitut Pasteur, Université Paris Cité, INSERM U1223, Équipe Labellisée Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France.
Emilie RassUniversité Paris-Saclay, INSERM, CEA, UMR Stabilité Génétique Cellules Souches et Radiations, F-92260 Fontenay-aux-Roses, France.
Olivier AristeGenoSplice, 75014 Paris, France.
Nicolas SiaudCNRS UMR 8200, Institut de Cancérologie Gustave-Roussy, Université Paris-Saclay, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
Benjamin RenoufGenome Dynamics in the Immune System Laboratory, Institut Imagine, INSERM, UMR 1163, Université Paris Descartes, Sorbonne Paris Cité, Equipe Labellisée Ligue Contre le Cancer, 75015 Paris, France.
Armel MilletGenome Dynamics in the Immune System Laboratory, Institut Imagine, INSERM, UMR 1163, Université Paris Descartes, Sorbonne Paris Cité, Equipe Labellisée Ligue Contre le Cancer, 75015 Paris, France.
Nadine PugetMCD, Centre de Biologie Intégrative (CBI), CNRS, Université de Toulouse, UT3, 31062 Toulouse, France.
Pascale BertrandUniversité Paris-Saclay, INSERM, CEA, UMR Stabilité Génétique Cellules Souches et Radiations, F-92260 Fontenay-aux-Roses, France.
Pierre de la GrangeGenoSplice, 75014 Paris, France.
Erika BrunetGenome Dynamics in the Immune System Laboratory, Institut Imagine, INSERM, UMR 1163, Université Paris Descartes, Sorbonne Paris Cité, Equipe Labellisée Ligue Contre le Cancer, 75015 Paris, France.ORCID 0000-0002-1726-4673
Ludovic DerianoInstitut Pasteur, Université Paris Cité, INSERM U1223, Équipe Labellisée Ligue Contre Le Cancer, Genome Integrity, Immunity and Cancer Unit, 75015 Paris, France.ORCID 0000-0002-9673-9525
Bernard S LopezUniversité de Paris Cité, INSERM U1016, UMR 8104 CNRS, Institut Cochin, 24 rue du Faubourg St. Jacques, 75014 Paris, France.ORCID 0000-0001-5088-0155

Funding

Fondation ARC ARCPJA2021060003792Fondation ARC ARCPJA2022060005157Institut National du Cancer PLBIO21-072Institut National du Cancer PLBIO24-196ITMO Cancer PCSI 2022LabEx Who Am I? ANR-11-LABX-0071LabEx Who Am I? Idex ANR-11-IDEX-0005-02La Ligue Contre Le Cancer
6 · The paper itself

Abstract

Genetic instability is a major hazard threatening the fate of cells and ultimately of organisms. DNA double-strand break (DSB) is a highly toxic lesion, jeopardizing genome stability. Using cytogenetic and differential exome sequencing, we show here that upregulation of the kinase PKB/AKT1 leads to genomic rearrangements and chromosome fusions. By combining various approaches, at the genome scale and at precise loci, we show that PKB/AKT1 stimulates DSB end-joining, leading to inter- and intrachromosomal genomic rearrangements. The MRE11-RAD50-NBS1 (MRN) complex plays an essential role in the early steps of DSB signaling/repair. We show here that PKB/AKT1 favors the assembly of MRN, leading to the stimulation of DSB signaling via the MRE11/ATM axis. We identify MRE11 as a phosphorylation effector of PKB/AKT1 and reveal several sites whose phosphorylation is required for PKB-mediated stimulation of DSB end-joining and chromosome fusions. These data reveal that PKB/AKT1 actively promotes genetic instability by increasing the efficiency of DSB end-joining through MRE11 phosphorylation on these sites. These results highlight that not only a defect of DSB signaling/repair but also its stimulation, can lead to genome rearrangements and underline the importance of a precise regulation of the DNA damage response to maintain genome stability.

Indexed as

DNA-Binding ProteinsDNA Breaks, Double-StrandedDNA End-Joining RepairGene RearrangementMRE11 Homologue ProteinProto-Oncogene Proteins c-aktAcid Anhydride HydrolasesAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsDNA Repair EnzymesGenomic InstabilityHumansNuclear ProteinsPhosphorylationSignal TransductionAcid Anhydride HydrolasesAKT1 protein, humanAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsDNA-Binding ProteinsDNA Repair EnzymesMRE11 Homologue ProteinMRE11 protein, humanNBN protein, humanNuclear ProteinsProto-Oncogene Proteins c-aktRAD50 protein, human

Identifiers

PMID40479710
PMCPMC12143594

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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.