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The restriction modification system (RM system) is used by bacteria, and perhaps other prokaryotic organisms, to protect themselves from foreign DNA, such as the one borne by bacteriophages. It was first discovered by Salvatore Luria and Mary Human in 1952 and 1953. They found that bacteriophage growing within an infected bacterium could be modified, so that upon their release and re-infection of a related bacterium the bacteriophage’s growth is restricted (inhibited) (also described by Luria in his autobiography on pages 45 and 99 in 1984).〔Salvator E Luria. A Slot Machine, A Broken Test Tube: An Autobiography. Harper & Row, New York: 1984. Pp. 228. ISBN 0-06-015260-5 (USA and Canada)〕 In 1953, Jean Weigle and Giuseppe Bertani reported similar examples of host-controlled modification using different bacteriophage systems. Later work by Daisy Dussoix and Werner Arber in 1962 and many other subsequent workers led to the understanding that restriction was due to attack and breakdown of the modified bacteriophage’s DNA by specific enzymes of the recipient bacteria. As reviewed by Daniel Nathans and Hamilton Smith in 1975, this work resulted in the discovery of the class of enzymes now known as Restriction enzymes. When these enzymes were isolated in the laboratory they could be used for controlled manipulation of DNA, thus providing the foundation for the development of genetic engineering. Werner Arber, Daniel Nathans, and Hamilton Smith were awarded the Nobel Prize in Physiology or Medicine in 1978 for their work on restriction-modification. Bacteria have restriction enzymes, also called restriction endonucleases, which cleave double stranded DNA at specific points into fragments, which are then degraded further by other endonucleases. This prevents infection by effectively destroying the foreign DNA introduced by an infectious agent (such as a bacteriophage). Approximately one quarter of known bacteria possess RM systems and of those about one half have more than one type of system. As the sequences recognized by the restriction enzymes are very short, the bacterium itself will almost certainly contain some within its genome. In order to prevent destruction of its own DNA by the restriction enzymes, methyl groups are added. These modifications must not interfere with the DNA base-pairing, and therefore, usually only a few specific bases are modified on each strand. Endonucleases cleave internal/non-terminal phosphodiester bonds. Restriction endonucleases cleave internal phosphodiester bonds only after recognising specific sequences in DNA which are usually 4-6 base pairs long, and often palindromic. ==Types of restriction modification system== There are five kinds of restriction modification system: type I, type II, type IIS, type III and type IV, all with restriction enzyme activity and a methylase activity. They were named in the order of discovery, although the type II system is the most common. Type I systems are the most complex, consisting of three polypeptides: R (restriction), M (modification), and S (specificity). The resulting complex can both cleave and methylate DNA. Both reactions require ATP, and cleavage often occurs a considerable distance from the recognition site. The S subunit determines the specificity of both restriction and methylation. Cleavage occurs at variable distances from the recognition sequence, so discrete bands are not easily visualized by gel electrophoresis. Type II systems are the simplest and the most prevalent. Instead of working as a complex, the methyltransferase and endonuclease are encoded as two separate proteins and act independently (there is no specificity protein). Both proteins recognize the same recognition site, and therefore compete for activity. The methyltransferase acts as a monomer, methylating the duplex one strand at a time. The endonuclease acts as a homodimer, which facilitates the cleavage of both strands. Cleavage occurs at a defined position close to or within the recognition sequence, thus producing discrete fragments during gel electrophoresis. For this reason, Type II systems are used in labs for DNA analysis and gene cloning. ''Neisseria meningitides'' has multiple type II restriction endonuclease systems that are employed in natural genetic transformation. Natural genetic transformation is a process by which a recipient bacterial cell can take up DNA from a neighboring donor bacterial cell and integrate this DNA into its genome by recombination. Although early work on restriction modification systems focused on the benefit to bacteria of protecting themselves against invading bacteriophage DNA or other foreign DNA, it is now known that these systems can also be used to restrict DNA introduced by natural transformation from other members of the same, or related species. In the pathogenic bacterium ''Neisseria meningitides'' (meningococci), competence for transformation is a highly evolved and complex process where multiple proteins at the bacterial surface, in the membranes and in the cytoplasm interact with the incoming transforming DNA. Restriction-modification systems are abundant in the genus ''Neisseria''. ''N. meningitides'' has multiple type II restriction endonuclease systems. The restriction modification systems in ''N. meningitides'' vary in specificity between different clades.〔 This specificity provides an efficient barrier against DNA exchange between clades.〔 Luria, on page 99 of his autobiography,〔 referred to such a restriction behavior as “an extreme instance of unfriendliness.” Restriction-modification appears to be a major driver of sexual isolation and speciation in the meningococci. Caugant and Miden suggested that restriction-modification systems in meningococci may act to allow genetic exchange among very close relatives while reducing (but not completely preventing) genetic exchange among meningococci belonging to different clonal complexes and related species. Type III systems have R and M proteins that form a complex of modification and cleavage. The M protein, however, can methylate on its own. Methylation also only occurs on one strand of the DNA unlike most other known mechanisms. The heterodimer formed by the R and M proteins competes with itself by modifying and restricting the same reaction. This results in incomplete digestion.〔Wilson, G., "(Organization of Restriction-Modification Systems ),"''Nucleic Acids Research'' (1991), Vol 19, pg2539-2566.〕〔Wilson, G., "(Restriction and Modification Systems )," ''Annual Review of Genetics'' (1991), 25:585-627.〕 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Restriction modification system」の詳細全文を読む スポンサード リンク
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