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==Episomes== {{main|Episome}} The term ''episome'' was introduced by [[François Jacob]] and [[Élie Wollman]] in 1958 to refer to extra-chromosomal genetic material that may replicate autonomously or become integrated into the chromosome.<ref>{{cite journal | vauthors = Morange M | title = What history tells us XIX. The notion of the episome | journal = Journal of Biosciences | volume = 34 | issue = 6 | pages = 845–848 | date = December 2009 | pmid = 20093737 | doi = 10.1007/s12038-009-0098-z | s2cid = 11367145 }}</ref><ref>{{citation |vauthors=Jacob F, Wollman EL |year=1958 |title= Les épisomes, elements génétiques ajoutés |journal=Comptes Rendus de l'Académie des Sciences de Paris |volume=247|issue=1 |pages= 154–56 |pmid= 13561654 }}</ref> Since the term was introduced, however, its use has changed, as ''plasmid'' has become the preferred term for autonomously replicating extrachromosomal DNA. At a 1968 symposium in London some participants suggested that the term ''episome'' be abandoned, although others continued to use the term with a shift in meaning.<ref>{{cite book |chapter-url=https://books.google.com/books?id=a1g7Xf4CTygC&pg=PA4 |title=Bacterial Episomes and Plasmids |publisher=CIBA Foundation Symposium | vauthors = Hayes W |chapter=What are episomes and plasmids? | veditors = Wolstenholme GE, O'Connor M |pages=4–8 |year=1969 |isbn=978-0700014057 }}</ref><ref>{{cite book |url=https://books.google.com/books?id=a1g7Xf4CTygC&pg=PA244 |title= Bacterial Episomes and Plasmids |publisher=CIBA Foundation Symposium | veditors = Wolstenholme GE, O'Connor M |pages=244–45 |year=1969 |isbn=978-0700014057 }}</ref> Today, some authors use ''episome'' in the context of prokaryotes to refer to a plasmid that is capable of integrating into the chromosome. The integrative plasmids may be replicated and stably maintained in a cell through multiple generations, but at some stage, they will exist as an independent plasmid molecule.<ref>{{cite book |url=https://books.google.com/books?id=byoWBAAAQBAJ&pg=PA238 |title=Introduction to Genetics: A Molecular Approach| vauthors = Brown TA |publisher=Garland Science |year= 2011 |page=238 |isbn=978-0815365099}}</ref> In the context of eukaryotes, the term ''episome'' is used to mean a non-integrated extrachromosomal closed circular DNA molecule that may be replicated in the nucleus.<ref>{{cite journal | vauthors = Van Craenenbroeck K, Vanhoenacker P, Haegeman G | title = Episomal vectors for gene expression in mammalian cells | journal = European Journal of Biochemistry | volume = 267 | issue = 18 | pages = 5665–5678 | date = September 2000 | pmid = 10971576 | doi = 10.1046/j.1432-1327.2000.01645.x | doi-access = }}</ref><ref>{{cite journal | vauthors = Colosimo A, Goncz KK, Holmes AR, Kunzelmann K, Novelli G, Malone RW, Bennett MJ, Gruenert DC | title = Transfer and expression of foreign genes in mammalian cells | journal = BioTechniques | volume = 29 | issue = 2 | pages = 314–18, 320–22, 324 passim | date = August 2000 | pmid = 10948433 | doi = 10.2144/00292rv01 | url = http://www9.georgetown.edu/gumc/departments/pharmacology/courses/Glazer1.pdf | doi-access = free | archive-url = https://web.archive.org/web/20110724082856/http://www9.georgetown.edu/gumc/departments/pharmacology/courses/Glazer1.pdf | archive-date = 24 July 2011 }}</ref> Viruses are the most common examples of this, such as [[herpesviridae|herpesviruses]], [[adenoviruses]], and [[polyomavirus]]es, but some are plasmids. Other examples include aberrant chromosomal fragments, such as [[double minute|double minute chromosomes]], that can arise during artificial gene amplifications or in pathologic processes (e.g., cancer cell transformation). Episomes in eukaryotes behave similarly to plasmids in prokaryotes in that the DNA is stably maintained and replicated with the host cell. Cytoplasmic viral episomes (as in [[poxvirus]] infections) can also occur. Some episomes, such as herpesviruses, replicate in a [[rolling circle]] mechanism, similar to [[bacteriophage]]s (bacterial phage viruses). Others replicate through a bidirectional replication mechanism (''Theta type'' plasmids). In either case, episomes remain physically separate from host cell chromosomes. Several cancer viruses, including [[Epstein-Barr virus]] and [[Kaposi's sarcoma-associated herpesvirus]], are maintained as latent, chromosomally distinct episomes in cancer cells, where the viruses express [[oncogenes]] that promote cancer cell proliferation. In cancers, these episomes passively replicate together with host chromosomes when the cell divides. When these viral episomes initiate [[lytic cycle|lytic replication]] to generate multiple virus particles, they generally activate cellular [[innate immunity]] defense mechanisms that kill the host cell.
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