Evidence map›Paper›PMID 33199619›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Exo1 recruits Cdc5 polo kinase to MutLγ to ensure efficient meiotic crossover formation.

Aurore Sanchez, Céline Adam, Felix Rauh, Yann Duroc, Lepakshi Ranjha, Bérangère Lombard, Xiaojing Mu, Mélody Wintrebert, Damarys Loew, Alba Guarné and 8 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

33 citing papers in PubMed, 43 citations in OpenAlex.

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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

18 authors at 7 institutions in 5 countries.

Aurore SanchezInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75005 Paris, France.
Céline AdamInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75005 Paris, France.
Felix RauhMax F. Perutz Laboratories, University of Vienna, 1010 Wien, Austria.
Yann DurocInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75005 Paris, France.ORCID 0000-0001-6665-3184
Lepakshi RanjhaInstitute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6501 Bellinzona, Switzerland.
Bérangère LombardInstitut Curie, Paris Sciences et Lettres Research University, 75006 Paris, France.ORCID 0000-0001-9044-3662
Xiaojing MuMolecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
Mélody WintrebertInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75005 Paris, France.ORCID 0000-0003-2803-8804
Damarys LoewInstitut Curie, Paris Sciences et Lettres Research University, 75006 Paris, France.ORCID 0000-0002-9111-8842
Alba GuarnéDepartment of Biochemistry, Centre de Recherche en Biologie Structurale, McGill University, Montreal, QC H3A 0G4, Canada.ORCID 0000-0003-4906-9132
Stefano GnanInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75005 Paris, France.
Chun-Long ChenInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75005 Paris, France.ORCID 0000-0002-4795-0295
Scott KeeneyMolecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065.ORCID 0000-0002-1283-6417
Petr CejkaInstitute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6501 Bellinzona, 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
Franz KleinMax F. Perutz Laboratories, University of Vienna, 1010 Wien, Austria.ORCID 0000-0001-7204-1432
Jean-Baptiste CharbonnierInstitute for Integrative Biology of the Cell (I2BC), Commissariat à l'Energie Atomique, CNRS, Université Paris-Sud, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
Valérie BordeInstitut Curie, Paris Sciences et Lettres Research University, CNRS, UMR3244, 75005 Paris, France; valerie.borde@curie.fr.ORCID 0000-0001-6520-2461
Centre National de la Recherche Scientifique · FRMemorial Sloan Kettering Cancer Center · USUniversità della Svizzera italiana · CHUniversité Paris Sciences et Lettres · FRUniversité Paris-Sud · FRUniversity of Vienna · ATMcGill University · CA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Mechanism and regulation of meiotic recombinationR35GM118092 · NIGMS · SLOAN-KETTERING INST CAN RESEARCH · PI Scott Keeney · 2016 to 2026
$7.0M
NCI NIH HHS P30 CA008748NIGMS NIH HHS R35 GM118092
6 · The paper itself

Abstract

Crossovers generated during the repair of programmed meiotic double-strand breaks must be tightly regulated to promote accurate homolog segregation without deleterious outcomes, such as aneuploidy. The Mlh1-Mlh3 (MutLγ) endonuclease complex is critical for crossover resolution, which involves mechanistically unclear interplay between MutLγ and Exo1 and polo kinase Cdc5. Using budding yeast to gain temporal and genetic traction on crossover regulation, we find that MutLγ constitutively interacts with Exo1. Upon commitment to crossover repair, MutLγ-Exo1 associate with recombination intermediates, followed by direct Cdc5 recruitment that triggers MutLγ crossover activity. We propose that Exo1 serves as a central coordinator in this molecular interplay, providing a defined order of interaction that prevents deleterious, premature activation of crossovers. MutLγ associates at a lower frequency near centromeres, indicating that spatial regulation across chromosomal regions reduces risky crossover events. Our data elucidate the temporal and spatial control surrounding a constitutive, potentially harmful, nuclease. We also reveal a critical, noncatalytic role for Exo1, through noncanonical interaction with polo kinase. These mechanisms regulating meiotic crossovers may be conserved across species.

Indexed as

Crossing Over, GeneticAmino Acid MotifsAmino Acid SequenceBinding SitesCell Cycle ProteinsChromosomes, FungalExodeoxyribonucleasesFungal ProteinsMeiosisModels, BiologicalModels, MolecularMutL ProteinsProtein BindingProtein ConformationProtein Interaction Domains and MotifsRecombination, GeneticCell Cycle ProteinsExodeoxyribonucleasesFungal ProteinsMutL ProteinscrossoversmeiosisMutLpolo kinaserecombination

Identifiers

PMID33199619
PMCPMC7720183
OpenAlexW3098968640

What OpenQuestion holds

Textmetadata
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.