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抗 CRISPR 蛋白:CRISPR-Cas 系统的蛋白抑制剂。

Anti-CRISPRs: Protein Inhibitors of CRISPR-Cas Systems.

机构信息

Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5G 1M1, Canada; email:

Department of Biochemistry, University of Toronto, Toronto, Ontario M5G 1M1, Canada; email:

出版信息

Annu Rev Biochem. 2020 Jun 20;89:309-332. doi: 10.1146/annurev-biochem-011420-111224. Epub 2020 Mar 18.

DOI:10.1146/annurev-biochem-011420-111224
PMID:32186918
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9718424/
Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR) together with their accompanying (CRISPR-associated) genes are found frequently in bacteria and archaea, serving to defend against invading foreign DNA, such as viral genomes. CRISPR-Cas systems provide a uniquely powerful defense because they can adapt to newly encountered genomes. The adaptive ability of these systems has been exploited, leading to their development as highly effective tools for genome editing. The widespread use of CRISPR-Cas systems has driven a need for methods to control their activity. This review focuses on anti-CRISPRs (Acrs), proteins produced by viruses and other mobile genetic elements that can potently inhibit CRISPR-Cas systems. Discovered in 2013, there are now 54 distinct families of these proteins described, and the functional mechanisms of more than a dozen have been characterized in molecular detail. The investigation of Acrs is leading to a variety of practical applications and is providing exciting new insight into the biology of CRISPR-Cas systems.

摘要

成簇规律间隔短回文重复序列(CRISPR)及其伴随的(CRISPR 相关)基因在细菌和古菌中频繁存在,用于防御入侵的外源 DNA,如病毒基因组。CRISPR-Cas 系统提供了一种独特而强大的防御机制,因为它们可以适应新遇到的基因组。这些系统的适应性已被开发利用,导致它们成为高效的基因组编辑工具。CRISPR-Cas 系统的广泛应用推动了对控制其活性的方法的需求。本综述重点介绍抗 CRISPR(Acrs),即由病毒和其他移动遗传元件产生的蛋白质,它们可以有效地抑制 CRISPR-Cas 系统。这些蛋白质在 2013 年被发现,目前已经描述了 54 种不同的家族,并且已经对十几个家族的功能机制进行了分子细节的描述。对 Acrs 的研究正在导致各种实际应用,并为 CRISPR-Cas 系统的生物学提供了令人兴奋的新见解。

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Tissue-restricted genome editing in vivo specified by microRNA-repressible anti-CRISPR proteins.通过 microRNA 抑制性抗 CRISPR 蛋白在体内进行组织受限的基因组编辑。
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Structural basis for AcrVA4 inhibition of specific CRISPR-Cas12a.
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