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Substrate Generation for Endonucleases of CRISPR/Cas Systems
Published on: September 8, 2012
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Diverse viral cas genes antagonize CRISPR immunity
Mark A Katz1, Edith M Sawyer1, Luke Oriolt1
1Department of Microbiology, University of Washington, Seattle, WA, USA.
Nature
|September 4, 2024
Summary
Researchers discovered new anti-CRISPR (Acr) proteins in Listeria that target bacterial CRISPR-Cas immune systems. These Acrs evolve from Cas genes, offering broad-spectrum control over genome editing technologies.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Prokaryotic CRISPR-Cas systems provide adaptive immunity against phages and plasmids.
- Anti-CRISPR proteins (Acrs) counteract CRISPR-Cas immunity by inhibiting Cas protein activity.
- The evolutionary origins and broad-spectrum inhibition mechanisms of Acrs remain largely unknown.
Purpose of the Study:
- Investigate Acr content and inhibition specificity in diverse Listeria isolates.
- Identify novel Acr gene families and their origins.
- Explore the evolution of Acrs through cas gene co-option.
Main Methods:
- Analysis of CRISPR-Cas systems in Listeria isolates.
- Identification and characterization of novel acr gene families.
- Probing viral sequence databases for orphan cas genes.
- Functional verification of identified Acrs and cas homologues.
Main Results:
- Discovered 11 new and 4 known acr gene families in Listeria, encoded by mobile elements.
- Identified two Acrs with homology to type I-B Cas proteins, one forming a defective interference complex.
- Found a type I-B Cas homologue inhibiting RNA-targeting type VI CRISPR via crRNA degradation.
- Verified a broad-spectrum cas3 homologue inhibiting types I-B, II-A, and VI-A CRISPR immunity.
Conclusions:
- Provided direct evidence for Acr evolution through cas gene co-option.
- Identified novel Acrs with potential for broad-spectrum control of genome editing technologies.
- Expanded understanding of CRISPR-Cas system subversion and evolution.
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