11 Ribonucleases H

11 Ribonucleases H
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11 核糖核酸酶 H

DOI:
10.1101/087969426.25.341
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发表时间:
1993
期刊:
Cold Spring Harbor Monograph Archive
影响因子:
--
通讯作者:
D. Matthews
D. Matthews
中科院分区:
--
文献类型:
--
作者:
Z. Hostomský;Z. Hostomska;D. Matthews

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I.核糖核酸酶H(RNase H)(核糖核酸[在RNA:DNA杂交体中] 5′-腺苷酸水解酶,E.C.3.1.26.4)特异性切割RNA:DNA杂交双链体中的RNA链。豪森和Stein(1970)引入名称H(表示杂交),以描述在小牛胸腺提取物中发现的一种新的核糖核酸酶活性(Stein和豪森,1969)。所有已知的具有RNase H活性的核酸酶都需要二价金属阳离子来水解RNA磷酸二酯键,产生5′-磷酸和3′-羟基末端。游离3′-羟基末端的存在使得所得RNA片段适合作为DNA聚合酶的引物。RNA酶H包括普遍存在的酶家族,在从细菌到哺乳动物的所有生物体中以多种形式检测到。然而,除了它们在逆转录病毒生命周期中的功能已被充分理解外,其他细胞RNA酶H的生物学作用还不太清楚。除了推测它们参与DNA复制之外,(以及分离的酶作为体外核酸操作试剂的实用性),具有可能的治疗意义的另外两个因素促成了最近对RNA酶H的兴趣增加:(1)内源性RNase H活性在反义寡核苷酸作用机制中的假定作用,以及(2)该酶作为抗病毒靶点的潜在重要性,特别是与人类免疫缺陷病毒(HIV)感染和获得性免疫缺陷综合征(AIDS)有关。自从Crouch和Dirksen(1982)首次全面概述RNases H以来,最近出现了两篇综述(Crouch 1990; Wintersberger 1990),涉及...
I. INTRODUCTION Ribonuclease H (RNase H) (Ribonucleate [in RNA:DNA hybrids] 5′-oligonucleotidohydrolase, E.C.3.1.26.4) specifically cleaves the RNA strand in an RNA:DNA hybrid duplex. The designation H (for hybrid) was introduced by Hausen and Stein (1970) to describe a new ribonuclease activity discovered in extracts from calf thymus (Stein and Hausen 1969). All known nucleases with RNase H activity require divalent metal cations for hydrolysis of the RNA phosphodiester bond producing 5′-phosphate and 3′-hydroxyl termini. The presence of the free 3′-hydroxyl terminus makes the resulting RNA fragment suitable as a primer for DNA polymerase. RNases H comprise a family of ubiquitous enzymes, detected in multiple forms in all organisms from bacteria to mammals. However, with the exception of their well-understood function in the life cycle of retroviruses, the biological roles of other cellular RNases H are much less clear. In addition to their presumed involvement in DNA replication (and the practical usefulness of the isolated enzyme as a reagent for in vitro manipulations with nucleic acids), two other factors with possible therapeutic implications have contributed to the recent increased interest in RNases H: (1) the presumed role of endogenous RNase H activity in the mechanism of action of antisense oligonucleotides and (2) the potential importance of the enzyme as an antiviral target, especially in connection with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Since the first comprehensive overview of RNases H by Crouch and Dirksen (1982), two more recent reviews have appeared (Crouch 1990; Wintersberger 1990) that deal with...