Evidence map›Paper›PMID 30107450›Full record

ArticleNucleic acids research2018

Role of nucleotide identity in effective CRISPR target escape mutations.

Tim Künne, Yifan Zhu, Fausia da Silva, Nico Konstantinides, Rebecca E McKenzie, Ryan N Jackson, Stan Jj Brouns

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.6field-weighted citation impact, top 31% 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

10 citing papers in PubMed, 18 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

7 authors at 3 institutions in 2 countries.

Tim KünneLaboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Yifan ZhuLaboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Fausia da SilvaLaboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Nico KonstantinidesLaboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Rebecca E McKenzieKavli Institute of Nanoscience, Department of Bionanoscience, Delft University of Technology, Van der Maasweg 9, 2629 HZ Delft, The Netherlands.
Ryan N JacksonDepartment of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT, USA.
Stan Jj BrounsLaboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Stippeneng 4, 6708 WE Wageningen, The Netherlands.
Wageningen University & Research · NLDelft University of Technology · NLUtah State University · US

Funding

European Research Council 639707
6 · The paper itself

Abstract

Prokaryotes use primed CRISPR adaptation to update their memory bank of spacers against invading genetic elements that have escaped CRISPR interference through mutations in their protospacer target site. We previously observed a trend that nucleotide-dependent mismatches between crRNA and the protospacer strongly influence the efficiency of primed CRISPR adaptation. Here we show that guanine-substitutions in the target strand of the protospacer are highly detrimental to CRISPR interference and interference-dependent priming, while cytosine-substitutions are more readily tolerated. Furthermore, we show that this effect is based on strongly decreased binding affinity of the effector complex Cascade for guanine-mismatched targets, while cytosine-mismatched targets only minimally affect target DNA binding. Structural modeling of Cascade-bound targets with mismatches shows that steric clashes of mismatched guanines lead to unfavorable conformations of the RNA-DNA duplex. This effect has strong implications for the natural selection of target site mutations that lead to effective escape from type I CRISPR-Cas systems.

Indexed as

CRISPR-Cas SystemsBase PairingBase SequenceClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCytosineDNA, BacterialDNA HelicasesEscherichia coliEscherichia coli ProteinsGuanineMutationPlasmidsRNA, BacterialRNA, Guide, CRISPR-Cas SystemsCRISPR-Associated ProteinsCytosineDNA, BacterialDNA HelicasesEscherichia coli ProteinsGuanineRNA, BacterialRNA, Guide, CRISPR-Cas SystemsygcB protein, E coli

Identifiers

PMID30107450
PMCPMC6212716
OpenAlexW2887757117

What OpenQuestion holds

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LicenceCC BY-NC
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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.