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His-Me 手指核酸酶的结构、机制和功能。

Structures, Mechanisms, and Functions of His-Me Finger Nucleases.

机构信息

Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan.

Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan; Graduate Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei 10048, Taiwan.

出版信息

Trends Biochem Sci. 2020 Nov;45(11):935-946. doi: 10.1016/j.tibs.2020.07.002. Epub 2020 Aug 14.

DOI:10.1016/j.tibs.2020.07.002
PMID:32807610
Abstract

His-Me finger (also called HNH or ββα-me) nucleases, are a large superfamily of nucleases that share limited sequence homology, but all members carry a highly similar catalytic motif exhibiting a ββα topology. This review represents a structural comparison of His-Me finger nucleases, summarizing their substrate-binding and recognition strategies, mechanisms of enzymatic hydrolysis, cellular functions, and the various means of activity regulation. His-Me finger nucleases usually function as monomers, making a single nick in nucleic acids to degrade foreign or host genomes, or as homodimers that introduce double-stranded DNA breaks for DNA restriction, integration, recombination, and repair. Various cellular neutralizing machineries have evolved to regulate the activity of His-Me finger nucleases, thereby maintaining genome integrity and cellular functionality.

摘要

他-我的手指(也称为 HNH 或 ββα-me)核酸酶是一个庞大的核酸酶超家族,它们具有有限的序列同源性,但所有成员都携带高度相似的催化基序,表现出 ββα 拓扑结构。这篇综述代表了 His-Me 手指核酸酶的结构比较,总结了它们的底物结合和识别策略、酶水解机制、细胞功能以及各种活性调节方式。His-Me 手指核酸酶通常作为单体发挥作用,在核酸上形成单个切口以降解外来或宿主基因组,或者作为同源二聚体形成双链 DNA 断裂以进行 DNA 限制、整合、重组和修复。各种细胞中和机制已经进化出来调节 His-Me 手指核酸酶的活性,从而维持基因组完整性和细胞功能。

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