ArticleeLife2019
The Cas4-Cas1-Cas2 complex mediates precise prespacer processing during CRISPR adaptation.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- CRISPR/Cas-Based Modifications for Therapeutic Applications: A Review.Molecular biotechnology · 2022Pooled it
- Article
- Type III CRISPR-Cas systems preferentially acquire spacers from early-expressed phage genes in a transcription-dependent manner.Nucleic acids research · 2026Article
- Insights into spacer acquisition of the type V-A CRISPR-Cas system of Francisella novicida U112.Nucleic acids research · 2026Article
- Structures reveal how the Cas1-2/3 integrase captures, delivers, and integrates foreign DNA into CRISPR loci.Structure (London, England : 1993) · 2025Article
- CRISPR-Cas Systems: A Functional Perspective and Innovations.International journal of molecular sciences · 2025Review
- Novel adaptive immune systems in pristine Antarctic soils.Scientific reports · 2025Article
- Functional insights into Solo-Cas4 inmicroLife · 2025Article
- Article
- Research Progress on the Mechanism and Application of the Type I CRISPR-Cas System.International journal of molecular sciences · 2024Review
- Mechanisms used for cDNA synthesis and site-specific integration of RNA into DNA genomes by a reverse transcriptase-Cas1 fusion protein.Science advances · 2024Article
- Harnessing CRISPR-Cas adaptation for RNA recording and beyond.BMB reports · 2024Review
- Biomaterial-Based CRISPR/Cas9 Delivery Systems for Tumor Treatment.Biomaterials research · 2024Article
- Mechanisms used for cDNA synthesis and site-specific integration of RNA into DNA genomes by a reverse transcriptase-Cas1 fusion protein.bioRxiv : the preprint server for biology · 2023Article
- CRISPR/Cas-Based Techniques for Live-Cell Imaging and Bioanalysis.International journal of molecular sciences · 2023Review
- Cas4/1 dual nuclease activities enable prespacer maturation and directional integration in a type I-G CRISPR-Cas system.bioRxiv : the preprint server for biology · 2023Article
- Genome expansion by a CRISPR trimmer-integrase.Nature · 2023Article
- Search for Origins of Anti-CRISPR Proteins by Structure Comparison.The CRISPR journal · 2023Article
- The biology and type I/III hybrid nature of type I-D CRISPR-Cas systems.The Biochemical journal · 2023Review
- CRISPR-Cas adaptation in Escherichia coli.Bioscience reports · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
CRISPR adaptation immunizes bacteria and archaea against viruses. During adaptation, the Cas1-Cas2 complex integrates fragments of invader DNA as spacers in the CRISPR array. Recently, an additional protein Cas4 has been implicated in selection and processing of prespacer substrates for Cas1-Cas2, although this mechanism remains unclear. We show that Cas4 interacts directly with Cas1-Cas2 forming a Cas4-Cas1-Cas2 complex that captures and processes prespacers prior to integration. Structural analysis of the Cas4-Cas1-Cas2 complex reveals two copies of Cas4 that closely interact with the two integrase active sites of Cas1, suggesting a mechanism for substrate handoff following processing. We also find that the Cas4-Cas1-Cas2 complex processes single-stranded DNA provided in cis or in trans with a double-stranded DNA duplex. Cas4 cleaves precisely upstream of PAM sequences, ensuring the acquisition of functional spacers. Our results explain how Cas4 cleavage coordinates with Cas1-Cas2 integration and defines the exact cleavage sites and specificity of Cas4.
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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.