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5-Methylcytosine
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== Discovery == While trying to isolate the bacterial [[toxin]] responsible for [[tuberculosis]], W.G. Ruppel isolated a novel [[nucleic acid]] named [[tuberculinic acid]] in 1898 from ''[[Mycobacterium tuberculosis|Tubercle bacillus]]''.<ref>{{cite book |vauthors = Matthews AP |year=2012 |url=https://books.google.com/books?id=809EPAAACAAJ|title= Physiological Chemistry |publisher= Williams & Wilkins Company/ |pages=167 |isbn=978-1130145373}}</ref> The nucleic acid was found to be unusual, in that it contained in addition to [[thymine]], [[guanine]] and [[cytosine]], a methylated nucleotide. In 1925, [[Treat Baldwin Johnson|Johnson]] and Coghill successfully detected a minor amount of a methylated cytosine derivative as a product of [[hydrolysis]] of tuberculinic acid with [[sulfuric acid]].<ref>{{cite journal |vauthors = Johnson TB, Coghill RD |year=1925 |title= The discovery of 5-methyl-cytosine in tuberculinic acid, the nucleic acid of the ''Tubercle bacillus'' |journal= J Am Chem Soc|volume=47 |issue=11|pages=2838β2844|doi=10.1021/ja01688a030}}</ref><ref>Grosjean H (2009). [https://www.ncbi.nlm.nih.gov/books/NBK6489/#A79016 Nucleic Acids Are Not Boring Long Polymers of Only Four Types of Nucleotides: A Guided Tour]. Landes Bioscience.</ref> This report was severely criticized because their identification was based solely on the optical properties of the crystalline [[picrate]], and other scientists failed to reproduce the same result.<ref>{{cite journal |vauthors = Vischer E, Zamenhof S, Chargaff E |year=1949 |title= Microbial nucleic acids: the desoxypentose nucleic acids of avian tubercle bacilli and yeast|journal= J Biol Chem|volume=177 |issue=1|pages=429β438|doi=10.1016/S0021-9258(18)57100-3 |pmid=18107446|doi-access=free}}</ref> But its existence was ultimately proven in 1948, when [[Rollin Douglas Hotchkiss|Hotchkiss]] separated the nucleic acids of [[DNA]] from [[calf (animal)|calf]] [[thymus]] using [[paper chromatography]], by which he detected a unique methylated cytosine, quite distinct from conventional cytosine and [[uracil]].<ref>{{cite journal |vauthors = Hotchkiss RD |year=1948|title= The quantitative separation of purines, pyrimidines and nucleosides by paper chromatography|journal=J Biol Chem|volume=175 |issue=1|pages=315β332|doi=10.1016/S0021-9258(18)57261-6|pmid=18873306|doi-access=free}}</ref> After seven decades, it turned out that it is also a common feature in different [[RNA]] molecules, although the precise role is uncertain.<ref>{{cite journal |vauthors = Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, Suter CM, Preiss T|year=2012|title= Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA|journal=Nucleic Acids Res|volume=40 |issue=11|pages=5023β5033|pmid=22344696|doi=10.1093/nar/gks144|pmc=3367185}}</ref>
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