Editing Restriction enzyme (section)

== History ==
[[File:GelDoc DNA gel electrophoresis photograph stained with ethidium bromide 03.jpg|thumb|Different restriction enzymes acting on different recognition sites produce different DNA fragments]]
The term restriction enzyme originated from the studies of [[lambda phage|phage λ]], a virus that infects bacteria, and the phenomenon of host-controlled restriction and modification of such bacterial phage or [[bacteriophage]].<ref>{{cite book |title=From Genes to Clones |author=Winnacker E-L |publisher=VCH |year=1987 |chapter=Chapter 2: Isolation, Identification, and Characterisation of DNA fragments |isbn=0-89573-614-4 |chapter-url=https://archive.org/details/fromgenestoclone0000winn }}</ref> The phenomenon was first identified in work done in the laboratories of [[Salvador Luria]], [[Jean Weigle]] and Giuseppe Bertani in the early 1950s.<ref name="Luria_Human_1952">{{cite journal | vauthors = Luria SE, Human ML | title = A nonhereditary, host-induced variation of bacterial viruses | journal = Journal of Bacteriology | volume = 64 | issue = 4 | pages = 557–69 | date = October 1952 | pmid = 12999684 | pmc = 169391 | doi = 10.1128/JB.64.4.557-569.1952 }}</ref><ref name="pmid13034700">{{cite journal | vauthors = Bertani G, Weigle JJ | title = Host controlled variation in bacterial viruses | journal = Journal of Bacteriology | volume = 65 | issue = 2 | pages = 113–21 | date = February 1953 | pmid = 13034700 | pmc = 169650 | doi = 10.1128/JB.65.2.113-121.1953 }}</ref>  It was found that, for a bacteriophage λ that can grow well in one strain of ''Escherichia coli'', for example ''E. coli'' C, when grown in another strain, for example ''E. coli'' K, its yields can drop significantly, by as much as three to five orders of magnitude. The host cell, in this example ''E. coli'' K, is known as the restricting host and appears to have the ability to reduce the biological activity of the phage λ. If a phage becomes established in one strain, the ability of that phage to grow also becomes restricted in other strains. In the 1960s, it was shown in work done in the laboratories of [[Werner Arber]] and [[Matthew Meselson]] that the restriction is caused by an enzymatic cleavage of the phage DNA, and the enzyme involved was therefore termed a restriction enzyme.<ref name="pmid4897066" /><ref name="pmid4868368">{{cite journal | vauthors = Meselson M, Yuan R | title = DNA restriction enzyme from E. coli | journal = Nature | volume = 217 | issue = 5134 | pages = 1110–4 | date = March 1968 | pmid = 4868368 | doi = 10.1038/2171110a0 | bibcode = 1968Natur.217.1110M | s2cid = 4172829 }}</ref><ref name="pmid13888713">{{cite journal | vauthors = Dussoix D, Arber W | title = Host specificity of DNA produced by Escherichia coli. II. Control over acceptance of DNA from infecting phage lambda | journal = Journal of Molecular Biology | volume = 5 | issue = 1 | pages = 37–49 | date = July 1962 | pmid = 13888713 | doi = 10.1016/S0022-2836(62)80059-X }}</ref><ref name="pmid14187389">{{cite journal | vauthors = Lederberg S, Meselson M | title = Degradation of non-replicating bacteriophage dna in non-accepting cells | journal = Journal of Molecular Biology | volume = 8 | issue = 5 | pages = 623–8 | date = May 1964 | pmid = 14187389 | doi = 10.1016/S0022-2836(64)80112-1 }}</ref>

The restriction enzymes studied by Arber and Meselson were type I restriction enzymes, which cleave DNA randomly away from the recognition site.<ref name="pmid15840723">{{cite journal | vauthors = Roberts RJ | title = How restriction enzymes became the workhorses of molecular biology | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 17 | pages = 5905–8 | date = April 2005 | pmid = 15840723 | pmc = 1087929 | doi = 10.1073/pnas.0500923102 | bibcode = 2005PNAS..102.5905R | doi-access = free }}</ref> In 1970, [[Hamilton O. Smith]], [[Thomas J. Kelly (scientist)|Thomas Kelly]] and Kent Wilcox isolated and characterized the first type II restriction enzyme, [[HindII]], from the bacterium ''[[Haemophilus influenzae]]''.<ref name="pmid5312500">{{cite journal | vauthors = Smith HO, Wilcox KW | title = A restriction enzyme from Hemophilus influenzae. I. Purification and general properties | journal = Journal of Molecular Biology | volume = 51 | issue = 2 | pages = 379–91 | date = July 1970 | pmid = 5312500 | doi = 10.1016/0022-2836(70)90149-X }}</ref><ref name="pmid5312501">{{cite journal | vauthors = Kelly TJ, Smith HO | title = A restriction enzyme from Hemophilus influenzae. II | journal = Journal of Molecular Biology | volume = 51 | issue = 2 | pages = 393–409 | date = July 1970 | pmid = 5312501 | doi = 10.1016/0022-2836(70)90150-6 }}</ref> Restriction enzymes of this type are more useful for laboratory work as they cleave DNA at the site of their recognition sequence and are the most commonly used as a molecular biology tool.<ref>{{cite journal | vauthors = Loenen WA, Dryden DT, Raleigh EA, Wilson GG, Murray NE | title = Highlights of the DNA cutters: a short history of the restriction enzymes | journal = Nucleic Acids Research | volume = 42 | issue = 1 | pages = 3–19 | date = January 2014 | pmid = 24141096 | pmc = 3874209 | doi = 10.1093/nar/gkt990 }}</ref> Later, [[Daniel Nathans]] and Kathleen Danna showed that cleavage of [[simian virus 40]] (SV40) DNA by restriction enzymes yields specific fragments that can be separated using [[polyacrylamide gel electrophoresis]], thus showing that restriction enzymes can also be used for mapping DNA.<ref name="pmid4332003">{{cite journal | vauthors = Danna K, Nathans D | title = Specific cleavage of simian virus 40 DNA by restriction endonuclease of Hemophilus influenzae | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 68 | issue = 12 | pages = 2913–7 | date = December 1971 | pmid = 4332003 | pmc = 389558 | doi = 10.1073/pnas.68.12.2913 | bibcode = 1971PNAS...68.2913D | doi-access = free }}</ref> For their work in the discovery and characterization of restriction enzymes, the 1978 [[Nobel Prize for Physiology or Medicine]] was awarded to [[Werner Arber]], [[Daniel Nathans]], and [[Hamilton O. Smith]].<ref name="urlMedicine 1978">{{cite web | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1978/ | title = The Nobel Prize in Physiology or Medicine | year = 1978 | publisher = The Nobel Foundation | quote = for the discovery of restriction enzymes and their application to problems of molecular genetics | access-date = 2008-06-07}}</ref> The discovery of restriction enzymes allows DNA to be manipulated, leading to the development of [[recombinant DNA]] technology that has many applications, for example, allowing the large scale production of proteins such as human [[insulin]] used by [[diabetes|diabetic]] patients.<ref name="Luria_Human_1952"/><ref name="pmid358198">{{cite journal | vauthors = Villa-Komaroff L, Efstratiadis A, Broome S, Lomedico P, Tizard R, Naber SP, Chick WL, Gilbert W | display-authors = 6 | title = A bacterial clone synthesizing proinsulin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 75 | issue = 8 | pages = 3727–31 | date = August 1978 | pmid = 358198 | pmc = 392859 | doi = 10.1073/pnas.75.8.3727 | bibcode = 1978PNAS...75.3727V | doi-access = free }}</ref>