Evidence map›Paper›PMID 29980759›Full record

ArticleScientific reports2018

Understanding the indirect DNA read-out specificity of I-CreI Meganuclease.

Jesús Prieto, Pilar Redondo, Blanca López-Méndez, Marco D'Abramo, Nekane Merino, Francisco J Blanco, Phillipe Duchateau, Guillermo Montoya, Rafael Molina

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future.International journal of molecular sciences · 2023
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  7. The genome editing revolution: review.Journal, genetic engineering & biotechnology · 2020
    Review
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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 at 5 institutions in 3 countries.

Jesús PrietoStructural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Macromolecular Crystallography Group, c/Melchor Fdez. Almagro 3, 28029, Madrid, Spain.
Pilar RedondoStructural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Cell Signalling and Adhesion Group, c/Melchor Fdez. Almagro 3, 28029, Madrid, Spain.ORCID 0000-0002-6723-0818
Blanca López-MéndezProtein Structure & Function Programme, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Marco D'AbramoDepartment of Chemistry, University of Rome "La Sapienza", Piazzale Aldo Moro 5, 00185, Rome, Italy.ORCID 0000-0001-6020-8581
Nekane MerinoCIC bioGUNE, Parque Tecnológico de Bizkaia Edificio 800, 48160, Derio, Spain.ORCID 0000-0003-0721-4813
Francisco J BlancoCIC bioGUNE, Parque Tecnológico de Bizkaia Edificio 800, 48160, Derio, Spain.ORCID 0000-0003-2545-4319
Phillipe DuchateauCELLECTIS S.A., 8 rue de la Croix Jarry, 75013, Paris, France.
Guillermo MontoyaProtein Structure & Function Programme, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
Rafael MolinaProtein Structure & Function Programme, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. rafael.molina@cpr.ku.dk.
University of Copenhagen · DKSpanish National Cancer Research Centre · ESCIC bioGUNE · ESIkerbasque · ESSapienza University of Rome · IT

Funding

EC | Seventh Framework Programme (European Union Seventh Framework Programme) N°283570Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness) CTQ-2014-56966-RMinisterio de Economía y Competitividad (Ministry of Economy and Competitiveness) JCI-2011-09308
6 · The paper itself

Abstract

The high DNA specificity of homing endonucleases makes them a powerful protein scaffold to engineer enzymes for genome manipulation. Understanding their molecular recognition of DNA is an important prerequisite to generate engineered enzymes able to cleave DNA in specific desired genome sites. Protein-DNA recognition studies have been mostly focused on specific direct contacts between amino acid side chains and bases to redesign the binding interface. However, the important role of indirect readout in the central region of the target DNA of the homing endonuclease I-CreI suggested that indirect readout may play a key role in the redesign of protein-DNA interactions. The sequences of the I-CreI central substrate region, 2NN, along with the adjacent 5NNN, are key for substrate cleavage. Here, we analyse the mechanism of target discrimination at the 5NNN region by the I-CreI protein, revealing its critical role in the location and occupancy of the catalytic metal ions, which is crucial for cleavage. Our data highlight the importance of indirect readout for target DNA cleavage, thus aiding I-CreI engineering when targeting new DNA sequences.

Indexed as

DNA CleavageBase SequenceBinding SitesCrystallizationDNADNA Restriction EnzymesModels, MolecularProtein ConformationSubstrate SpecificityDNADNA Restriction Enzymesendodeoxyribonuclease CreI

Identifiers

PMID29980759
PMCPMC6035192
OpenAlexW2810299170

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.