ArticleNature structural & molecular biology2022
CRISPR-Cas9 bends and twists DNA to read its sequence.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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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.
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.
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Who cites it
59 citing papers in PubMed.
- In-vivo CRISPR/Base-Editing "One-Shot" Therapies Targeting PCSK9.Current atherosclerosis reports · 2026Review
- Architecture of a DNA-guided Cas12a.Nature structural & molecular biology · 2026Article
- Exchange dynamics and kinetic control of gene regulation complexes.Nature reviews. Molecular cell biology · 2026Review
- A dynamically frustrated allosteric checkpoint consistent with conformational proofreading in CRISPR-Cas9.Nucleic acids research · 2026Article
- HIV cure: from early therapies to cutting-edge strategies.Journal of neurovirology · 2026Review
- Structure and evolution-guided design of minimal RNA-guided nucleases.Science (New York, N.Y.) · 2026Article
- Structural basis of AtCas9 recognition of PAM mutants in underwound DNA topology.Nature structural & molecular biology · 2026Article
- Harnessing Deep Learning Models for Guide RNA Optimization and Off-Target Prediction in CRISPR Systems.Biotechnology journal · 2026Review
- DNA-guided CRISPR-Cas12a effectors for programmable RNA recognition and cleavage.Nature biotechnology · 2026Article
- Article
- Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026Article
- Chemical control of 2'-hydroxyl-dependent Cas9 target engagement enables CRISPR RNA ribose replacement.bioRxiv : the preprint server for biology · 2026Article
- Structural and functional bases of F. rodentium Cas9 provide insights into CRISPR-Cas protein engineering.Cell genomics · 2026Article
- Better data for better predictions: data curation improves deep learning for sgRNA/Cas9 prediction.PeerJ · 2026Article
- Structure and evolution-guided design of minimal RNA-guided nucleases.bioRxiv : the preprint server for biology · 2025Article
- Structural and functional insights into internal domain replacement in SpCas9 for protein engineering.Scientific reports · 2025Article
- Article
- And… cut! - how conformational regulation of CRISPR-Cas effectors directs nuclease activity.The Biochemical journal · 2025Review
- Off-target interactions in the CRISPR-Cas9 Machinery: mechanisms and outcomes.Biochemistry and biophysics reports · 2025Review
- Programmable genome engineering and gene modifications for plant biodesign.Plant communications · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
In bacterial defense and genome editing applications, the CRISPR-associated protein Cas9 searches millions of DNA base pairs to locate a 20-nucleotide, guide RNA-complementary target sequence that abuts a protospacer-adjacent motif (PAM). Target capture requires Cas9 to unwind DNA at candidate sequences using an unknown ATP-independent mechanism. Here we show that Cas9 sharply bends and undertwists DNA on PAM binding, thereby flipping DNA nucleotides out of the duplex and toward the guide RNA for sequence interrogation. Cryogenic-electron microscopy (cryo-EM) structures of Cas9-RNA-DNA complexes trapped at different states of the interrogation pathway, together with solution conformational probing, reveal that global protein rearrangement accompanies formation of an unstacked DNA hinge. Bend-induced base flipping explains how Cas9 'reads' snippets of DNA to locate target sites within a vast excess of nontarget DNA, a process crucial to both bacterial antiviral immunity and genome editing. This mechanism establishes a physical solution to the problem of complementarity-guided DNA search and shows how interrogation speed and local DNA geometry may influence genome editing efficiency.
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Registered trials
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.