Structural biology of CRISPR-Cas immunity and genome editing enzymes

被引:98
|
作者
Wang, Joy Y. [1 ,2 ]
Pausch, Patrick [3 ]
Doudna, Jennifer A. [1 ,2 ,4 ,5 ,6 ,7 ,8 ,9 ]
机构
[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Innovat Genom Inst, Berkeley, CA 94720 USA
[3] Vilnius Univ, Life Sci Ctr, VU LSC EMBL Partnership Genome Editing Technol, Vilnius, Lithuania
[4] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA
[5] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA
[6] Univ Calif Berkeley, Calif Inst Quantitat Biosci QB3, Berkeley, CA 94720 USA
[7] Lawrence Berkeley Natl Lab, MBIB Div, Berkeley, CA USA
[8] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA
[9] Gladstone UCSF Inst Genom Immunol, San Francisco, CA USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
RNA-GUIDED ENDONUCLEASE; TARGET DNA RECOGNITION; R-LOOP COMPLEX; SPACER ACQUISITION; CONFORMATIONAL CONTROL; PAM RECOGNITION; FUNCTIONAL-CHARACTERIZATION; ADAPTIVE IMMUNITY; CRYSTAL-STRUCTURE; STRUCTURE REVEALS;
D O I
10.1038/s41579-022-00739-4
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
CRISPR-Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, we examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR-Cas immune systems and deployed for wide-ranging genome editing applications. We explore the adaptive and interference aspects of CRISPR-Cas function as well as open questions about the molecular mechanisms responsible for genome targeting. These structural insights reflect close evolutionary links between CRISPR-Cas systems and mobile genetic elements, including the origins and evolution of CRISPR-Cas systems from DNA transposons, retrotransposons and toxin-antitoxin modules. We discuss how the evolution and structural diversity of CRISPR-Cas systems explain their functional complexity and utility as genome editing tools. CRISPR-Cas systems provide resistance against foreign mobile genetic elements and have a wide range of genome editing and biotechnological applications. In this Review, Wang, Pausch and Doudna examine recent advances in understanding the molecular structures and mechanisms of enzymes comprising bacterial RNA-guided CRISPR-Cas immune systems and deployed for wide-ranging genome editing applications.
引用
收藏
页码:641 / 656
页数:16
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