Evidence map›Paper›PMID 40319035›Full record

ArticleNature communications2025

EXO1 promotes the meiotic MLH1-MLH3 endonuclease through conserved interactions with MLH1, MSH4 and DNA.

Megha Roy, Aurore Sanchez, Raphael Guerois, Issam Senoussi, Arianna Cerana, Jacopo Sgrignani, Andrea Cavalli, Andrea Rinaldi, Petr Cejka

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
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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

9 authors.

Megha Roy *Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland.ORCID http://orcid.org/0009-0001-7053-1195
Aurore Sanchez *Institute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland. aurore.sanchez@curie.fr.ORCID http://orcid.org/0009-0000-8949-2379
Raphael GueroisUniversité Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.ORCID http://orcid.org/0000-0001-5294-2858
Issam SenoussiInstitute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland.
Arianna CeranaInstitute of Oncology Research, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland.
Jacopo SgrignaniInstitute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland.
Andrea CavalliInstitute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland.ORCID http://orcid.org/0000-0003-4063-4502
Andrea RinaldiInstitute of Oncology Research, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland.
Petr CejkaInstitute for Research in Biomedicine, Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Bellinzona, Switzerland. petr.cejka@irb.usi.ch.ORCID http://orcid.org/0000-0002-9087-032X

Funding

EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 101018257Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_205199Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_207588
6 · The paper itself

Abstract

The endonuclease activity of MLH1-MLH3 (MutLγ) is stimulated by MSH4-MSH5 (MutSγ), EXO1, and RFC-PCNA to resolve meiotic recombination intermediates such as double Holliday junctions (HJs) into crossovers. We show that EXO1 directly interacts with MLH1 via the EXO1 MIP motif and a patch centered around EXO1-I403. Disrupting this interaction unexpectedly only partially inhibited MutLγ. We found that EXO1 also directly interacts with MutSγ. Crucially, a single point mutation in EXO1 (W371E) impairs its interaction with MSH4 and completely abolished its ability to activate DNA nicking by MutLγ without affecting its intrinsic nuclease function. Finally, disrupting magnesium coordinating residues in the nuclease domain of EXO1 has no impact on MutSγ-MutLγ activity, while the integrity of EXO1 residues mediating interactions with double-stranded DNA (dsDNA) is important. Our findings suggest EXO1 is an integral structural component of the meiotic resolvase complex, supported by conserved interactions with MutSγ, MutLγ and dsDNA. We propose that EXO1 helps tether MutSγ-MutLγ to dsDNA downstream of HJ recognition to promote DNA cleavage.

Indexed as

DNADNA-Binding ProteinsExodeoxyribonucleasesMeiosisMutL Protein Homolog 1MutL ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsDNA, CruciformDNA Repair EnzymesHumansProtein BindingDNADNA-Binding ProteinsDNA, CruciformDNA Repair EnzymesEXO1 protein, humanexodeoxyribonuclease IExodeoxyribonucleasesMLH1 protein, S cerevisiaeMutL Protein Homolog 1MutL ProteinsSaccharomyces cerevisiae Proteins

Identifiers

PMID40319035
PMCPMC12049449

What Socratic 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 Socratic graph.