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Molecular architectures and mechanisms of Class 2 CRISPR-associated nucleases


Garcia-Doval, Carmela; Jinek, Martin (2017). Molecular architectures and mechanisms of Class 2 CRISPR-associated nucleases. Current Opinion in Structural Biology, 47:157-166.

Abstract

Prokaryotic Class 2 CRISPR-Cas systems mediate adaptive immunity against invasive genetic elements by means of standalone effector proteins that function as RNA-guided nucleases. The effectors Cas9 and Cas12 generate double-strand breaks in DNA substrates, which has been exploited for genome editing applications. In turn, Cas13 enzymes function as RNA-guided ribonucleases whose non-specific activity is triggered by target RNA binding. In this review, we highlight recent structural investigations of Cas9, Cas12 and Cas13 nucleases that have illuminated many aspects of their molecular mechanisms. In particular, these studies have highlighted the role of guide RNA seed sequences in facilitating target recognition and the importance of conformational transitions in controlling target binding and cleavage.

Abstract

Prokaryotic Class 2 CRISPR-Cas systems mediate adaptive immunity against invasive genetic elements by means of standalone effector proteins that function as RNA-guided nucleases. The effectors Cas9 and Cas12 generate double-strand breaks in DNA substrates, which has been exploited for genome editing applications. In turn, Cas13 enzymes function as RNA-guided ribonucleases whose non-specific activity is triggered by target RNA binding. In this review, we highlight recent structural investigations of Cas9, Cas12 and Cas13 nucleases that have illuminated many aspects of their molecular mechanisms. In particular, these studies have highlighted the role of guide RNA seed sequences in facilitating target recognition and the importance of conformational transitions in controlling target binding and cleavage.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:3 November 2017
Deposited On:05 Dec 2017 15:05
Last Modified:19 Feb 2018 09:29
Publisher:Elsevier
ISSN:0959-440X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.sbi.2017.10.015
PubMed ID:29107822

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