Rao D N, Saha S, Krishnamurthy V
Department of Biochemistry, Indian Institute of Science, Bangalore, India.
Prog Nucleic Acid Res Mol Biol. 2000;64:1-63. doi: 10.1016/s0079-6603(00)64001-1.
The phenomenon of restriction and modification (R-M) was first observed in the course of studies on bacteriophages in the early 1950s. It was only in the 1960s that work of Arber and colleagues provided a molecular explanation for the host specificity. DNA restriction and modification enzymes are responsible for the host-specific barriers to interstrain and interspecies transfer of genetic information that have been observed in a variety of bacterial cell types. R-M systems comprise an endonuclease and a methyltransferase activity. They serve to protect bacterial cells against bacteriophage infection, because incoming foreign DNA is specifically cleaved by the restriction enzyme if it contains the recognition sequence of the endonuclease. The DNA is protected from cleavage by a specific methylation within the recognition sequence, which is introduced by the methyltransferase. Classic R-M systems are now divided into three types on the basis of enzyme complexity, cofactor requirements, and position of DNA cleavage, although new systems are being discovered that do not fit readily into this classification. This review concentrates on multisubunit, multifunctional ATP-dependent restriction enzymes. A growing number of these enzymes are being subjected to biochemical and genetic studies that, when combined with ongoing structural analyses, promise to provide detailed models for mechanisms of DNA recognition and catalysis. It is now clear that DNA cleavage by these enzymes involves highly unusual modes of interaction between the enzymes and their substrates. These unique features of mechanism pose exciting questions and in addition have led to the suggestion that these enzymes may have biological functions beyond that of restriction and modification. The purpose of this review is to describe the exciting developments in our understanding of how the ATP-dependent restriction enzymes recognize specific DNA sequences and cleave or modify DNA.
限制与修饰（R-M）现象最早是在20世纪50年代初对噬菌体的研究过程中观察到的。直到20世纪60年代，阿伯及其同事的研究才对宿主特异性给出了分子解释。DNA限制酶和修饰酶造成了在多种细菌细胞类型中观察到的遗传信息跨菌株和跨物种转移的宿主特异性障碍。R-M系统包括一种内切核酸酶和一种甲基转移酶活性。它们用于保护细菌细胞免受噬菌体感染，因为如果外来DNA包含内切核酸酶的识别序列，它就会被限制酶特异性切割。通过甲基转移酶引入的识别序列内的特定甲基化可保护DNA不被切割。经典的R-M系统现在根据酶的复杂性、辅因子需求和DNA切割位置分为三种类型，不过仍不断有新系统被发现，它们并不容易归入这一分类。本综述集中讨论多亚基、多功能的ATP依赖型限制酶。越来越多的这类酶正在接受生化和遗传学研究，这些研究与正在进行的结构分析相结合，有望为DNA识别和催化机制提供详细模型。现在很清楚，这些酶切割DNA涉及酶与其底物之间非常特殊的相互作用模式。这些独特的机制特征提出了令人兴奋的问题，此外还引发了这样一种观点，即这些酶可能具有超出限制与修饰的生物学功能。本综述的目的是描述我们在理解ATP依赖型限制酶如何识别特定DNA序列以及切割或修饰DNA方面所取得的令人兴奋的进展。
