Publications by authors named "J van Der Oost"
Biology and applications of CRISPR-Cas12 and transposon-associated homologs.
Nat Biotechnol
December 2024
Article Synopsis
- - Cas12 proteins are diverse nucleic acid-targeting proteins that utilize RNA guides and a single nuclease domain to target DNA and occasionally RNA.
- - Their high variability is the result of different evolutionary paths from transposon-related ancestors, leading to significant differences in size, structure, and function among various Cas12 variants.
- - The article reviews the unique characteristics of both natural and engineered Cas12 proteins, outlines their applications in genome editing and diagnostics, and explores future research directions.
The generation of cyclic oligoadenylates and subsequent allosteric activation of proteins that carry sensory domains is a distinctive feature of type III CRISPR-Cas systems. In this work, we characterize a set of associated genes of a type III-B system from that contains two caspase-like proteases, SAVED-CHAT and PCaspase (prokaryotic caspase), co-opted from a cyclic oligonucleotide-based antiphage signaling system (CBASS). Cyclic tri-adenosine monophosphate (AMP)-induced oligomerization of SAVED-CHAT activates proteolytic activity of the CHAT domains, which specifically cleave and activate PCaspase.
View Article and Find Full Text PDFAnti-CRISPR proteins (Acrs) block the activity of CRISPR-associated (Cas) proteins, either by inhibiting DNA interference or by preventing crRNA loading and complex formation. Although the main use of Acrs in genome engineering applications is to lower the cleavage activity of Cas proteins, they can also be instrumental for various other CRISPR-based applications. Here, we explore the genome editing potential of the thermoactive type II-C Cas9 variants from Geobacillus thermodenitrificans T12 (ThermoCas9) and Geobacillus stearothermophilus (GeoCas9) in Escherichia coli.
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- RNA-guided type V CRISPR-Cas12 effectors, like Cas12m2, help bacteria and archaea defend against mobile genetic elements by silencing their transcription through strong DNA binding, despite lacking the ability to cleave dsDNA.
- Researchers used cryo-electron microscopy to analyze Cas12m2 complexes with CRISPR RNA and target DNA, revealing how the complex forms and binds tightly to specific DNA regions.
- The study suggests that the structural features of Cas12m2, especially its unique REC and RuvC domains, play key roles in its adaptive immunity and inform the evolutionary relationship between Cas12 and its ancestor, TnpB.
Clostridium species are re-emerging as biotechnological workhorses for industrial acetone-butanol-ethanol production. This re-emergence is largely due to advances in fermentation technologies but also due to advances in genome engineering and re-programming of the native metabolism. Several genome engineering techniques have been developed including the development of numerous CRISPR-Cas tools.
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