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Conformational control of DNA target cleavage by CRISPR–Cas9

Overview of attention for article published in Nature, October 2015
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • Good Attention Score compared to outputs of the same age and source (67th percentile)

Mentioned by

news
13 news outlets
blogs
2 blogs
twitter
57 tweeters
patent
20 patents
facebook
1 Facebook page

Citations

dimensions_citation
260 Dimensions

Readers on

mendeley
704 Mendeley
citeulike
3 CiteULike
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Title
Conformational control of DNA target cleavage by CRISPR–Cas9
Published in
Nature, October 2015
DOI 10.1038/nature15544
Pubmed ID
Authors

Samuel H. Sternberg, Benjamin LaFrance, Matias Kaplan, Jennifer A. Doudna

Abstract

Cas9 is an RNA-guided DNA endonuclease that targets foreign DNA for destruction as part of a bacterial adaptive immune system mediated by clustered regularly interspaced short palindromic repeats (CRISPR). Together with single-guide RNAs, Cas9 also functions as a powerful genome engineering tool in plants and animals, and efforts are underway to increase the efficiency and specificity of DNA targeting for potential therapeutic applications. Studies of off-target effects have shown that DNA binding is far more promiscuous than DNA cleavage, yet the molecular cues that govern strand scission have not been elucidated. Here we show that the conformational state of the HNH nuclease domain directly controls DNA cleavage activity. Using intramolecular Förster resonance energy transfer experiments to detect relative orientations of the Cas9 catalytic domains when associated with on- and off-target DNA, we find that DNA cleavage efficiencies scale with the extent to which the HNH domain samples an activated conformation. We furthermore uncover a surprising mode of allosteric communication that ensures concerted firing of both Cas9 nuclease domains. Our results highlight a proofreading mechanism beyond initial protospacer adjacent motif (PAM) recognition and RNA-DNA base-pairing that serves as a final specificity checkpoint before DNA double-strand break formation.

Twitter Demographics

The data shown below were collected from the profiles of 57 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 704 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 4 <1%
United States 4 <1%
Germany 3 <1%
Switzerland 2 <1%
Brazil 2 <1%
Mexico 1 <1%
Finland 1 <1%
Netherlands 1 <1%
Canada 1 <1%
Other 7 <1%
Unknown 678 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 193 27%
Researcher 123 17%
Student > Bachelor 113 16%
Student > Master 92 13%
Student > Doctoral Student 37 5%
Other 82 12%
Unknown 64 9%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 254 36%
Agricultural and Biological Sciences 246 35%
Chemistry 40 6%
Medicine and Dentistry 19 3%
Engineering 19 3%
Other 54 8%
Unknown 72 10%

Attention Score in Context

This research output has an Altmetric Attention Score of 147. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 January 2020.
All research outputs
#134,948
of 15,879,709 outputs
Outputs from Nature
#10,782
of 75,801 outputs
Outputs of similar age
#3,294
of 287,090 outputs
Outputs of similar age from Nature
#351
of 1,073 outputs
Altmetric has tracked 15,879,709 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 75,801 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 85.8. This one has done well, scoring higher than 85% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 287,090 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 1,073 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.