Editing Repeated sequence (DNA) (section)

== Types and functions ==

Many repeat sequences are likely to be non-functional, decaying remnants of [[Transposable element]]s, these have been labelled "[[Junk DNA|junk]]" or "[[Selfish genetic element|selfish]]" DNA.<ref>{{cite journal | vauthors = Ohno S | title = So much "junk" DNA in our genome | journal = Brookhaven Symposia in Biology | volume = 23 | pages = 366–370 | date = 1972 | pmid = 5065367 }}</ref><ref>{{cite journal | vauthors = Orgel LE, Crick FH, Sapienza C | title = Selfish DNA | journal = Nature | volume = 288 | issue = 5792 | pages = 645–6 | date = December 1980 | pmid = 7453798 | doi = 10.1038/288645a0 | s2cid = 4370178 | bibcode = 1980Natur.288..645O }}</ref><ref>{{cite journal | vauthors = Palazzo AF, Gregory TR | title = The case for junk DNA | journal = PLOS Genetics | volume = 10 | issue = 5 | pages = e1004351 | date = May 2014 | pmid = 24809441 | doi = 10.1371/journal.pgen.1004351 | pmc = 4014423 | doi-access = free }}</ref> Nevertheless, occasionally some repeats may be [[Exaptation|exapted]] for other functions.<ref>{{cite journal | vauthors = Joly-Lopez Z, Bureau TE | title = Exaptation of transposable element coding sequences | journal = Current Opinion in Genetics & Development | volume = 49 | pages = 34–42 | date = April 2018 | pmid = 29525543 | doi = 10.1016/j.gde.2018.02.011 }}</ref>

=== Tandem repeats ===
[[Tandem repeat]]s are repeated sequences which are directly adjacent to each other in the genome.<ref>{{Cite web |title=Tandem Repeat |url=https://www.genome.gov/genetics-glossary/Tandem-Repeat |access-date=2022-09-30 |website=Genome.gov |language=en}}</ref> Tandem repeats may vary in the number of nucleotides comprising the repeated sequence, as well as the number of times the sequence repeats. When the repeating sequence is only 2–10 nucleotides long, the repeat is referred to as a short tandem repeat (STR) or [[microsatellite]].<ref>{{cite journal | vauthors = Sznajder ŁJ, Swanson MS | title = Short Tandem Repeat Expansions and RNA-Mediated Pathogenesis in Myotonic Dystrophy | journal = International Journal of Molecular Sciences | volume = 20 | issue = 13 | pages = 3365 | date = July 2019 | pmid = 31323950 | pmc = 6651174 | doi = 10.3390/ijms20133365 | doi-access = free }}</ref> When the repeating sequence is 10–60 nucleotides long, the repeat is referred to as a [[minisatellite]].<ref>{{Cite web |title=Minisatellite Repeats (MeSH Descriptor Data 2024) |id=D018598 |url=https://meshb.nlm.nih.gov/record/ui?name=Minisatellite |work=Medical Subject Headings |publisher=National Library of Medicine }}</ref> For minisatellites and microsatellites, the number of times the sequence repeats at a single locus can range from twice to hundreds of times.

Tandem repeats have a wide variety of biological functions in the genome. For example, minisatellites are often hotspots of meiotic [[homologous recombination]] in eukaryotic organisms.<ref name=Wahls98>{{cite journal | vauthors = Wahls WP | title = Meiotic recombination hotspots: shaping the genome and insights into hypervariable minisatellite DNA change | journal = Current Topics in Developmental Biology | volume = 37 | pages = 37–75 | date = 1998 | pmid = 9352183 | pmc = 3151733 | doi = 10.1016/s0070-2153(08)60171-4 | isbn = 9780121531379 }}</ref> Recombination is when two homologous chromosomes align, break, and rejoin to swap pieces. Recombination is important as a source of genetic diversity, as a mechanism for repairing damaged DNA, and a necessary step in the appropriate segregation of chromosomes in meiosis.<ref name=Wahls98 /> The presence of repeated sequence DNA makes it easier for areas of homology to align, thereby controlling when and where recombination occurs.

In addition to playing an important role in recombination, tandem repeats also play important structural roles in the genome. For example, [[telomere]]s are composed mainly of tandem TTAGGG repeats.<ref>{{cite journal | vauthors = Janssen A, Colmenares SU, Karpen GH | title = Heterochromatin: Guardian of the Genome | journal = Annual Review of Cell and Developmental Biology | volume = 34 | issue = 1 | pages = 265–288 | date = October 2018 | pmid = 30044650 | doi = 10.1146/annurev-cellbio-100617-062653 | s2cid = 51718804 | url = http://www.escholarship.org/uc/item/7294g81k | doi-access = free }}</ref> These repeats fold into highly organized [[G-quadruplex|G quadruplex]] structures which protect the ends of chromosomal DNA from degradation.<ref name=Qi05>{{cite journal | vauthors = Qi J, Shafer RH | title = Covalent ligation studies on the human telomere quadruplex | journal = Nucleic Acids Research | volume = 33 | issue = 10 | pages = 3185–92 | date = 2005-06-02 | pmid = 15933211 | pmc = 1142406 | doi = 10.1093/nar/gki632 }}</ref> Repetitive elements are enriched in the middle of chromosomes as well. [[Centromere]]s are the highly compact regions of chromosomes which join sister chromatids together and also allow the mitotic spindle to attach and separate sister chromatids during cell division.<ref>{{Cite web |title=Centromere |url=https://www.genome.gov/genetics-glossary/Centromere |access-date=2022-09-30 |website=Genome.gov |language=en}}</ref> Centromeres are composed of a 177 base pair tandem repeat named the α-satellite repeat.<ref name=Qi05 /> Pericentromeric heterochromatin, the DNA which surrounds the centromere and is important for structural maintenance, is composed of a mixture of different satellite subfamilies including the α-, β- and γ-satellites as well as HSATII, HSATIII, and sn5 repeats.<ref>{{cite journal | vauthors = Miga KH | title = Completing the human genome: the progress and challenge of satellite DNA assembly | journal = Chromosome Research | volume = 23 | issue = 3 | pages = 421–6 | date = September 2015 | pmid = 26363799 | doi = 10.1007/s10577-015-9488-2 | s2cid = 15229421 }}</ref>
[[File:Tandem_and_interspersed_repeat_schematic.png|thumb|350x350px|Tandem and interspersed repeat]]
Some repetitive sequences, such as those with structural roles discussed above, play roles necessary for proper biological functioning. Other tandem repeats have deleterious roles which drive diseases. Many other tandem repeats, however, have unknown or poorly understood functions.<ref>{{cite journal | vauthors = Padeken J, Zeller P, Gasser SM | title = Repeat DNA in genome organization and stability | journal = Current Opinion in Genetics & Development | volume = 31 | pages = 12–19 | date = April 2015 | pmid = 25917896 | doi = 10.1016/j.gde.2015.03.009 | series = Genome architecture and expression }}</ref>

=== Interspersed repeats ===
[[Interspersed repeat]]s are identical or similar DNA sequences which are found in different locations throughout the genome.<ref>{{Cite web |title=Interspersed repetitive sequences - Latest research and news {{!}} Nature |url=https://www.nature.com/subjects/interspersed-repetitive-sequences |access-date=2022-09-30 |website=www.nature.com}}</ref> Interspersed repeats are distinguished from tandem repeats in that the repeated sequences are not directly adjacent to each other but instead may be scattered among different chromosomes or far apart on the same chromosome. Most interspersed repeats are [[transposable element]]s (TEs), mobile sequences which can be "cut and pasted" or "copied and pasted" into different places in the genome.<ref name=Wicker07>{{cite journal | vauthors = Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy P, Morgante M, Panaud O, Paux E, SanMiguel P, Schulman AH | display-authors = 6 | title = A unified classification system for eukaryotic transposable elements | journal = Nature Reviews. Genetics | volume = 8 | issue = 12 | pages = 973–982 | date = December 2007 | pmid = 17984973 | doi = 10.1038/nrg2165 | s2cid = 32132898 }}</ref> TEs were originally called "jumping genes" for their ability to move, yet this term is somewhat misleading as not all TEs are discrete genes.<ref name=Nicolau21>{{cite journal | vauthors = Nicolau M, Picault N, Moissiard G | title = The Evolutionary Volte-Face of Transposable Elements: From Harmful Jumping Genes to Major Drivers of Genetic Innovation | journal = Cells | volume = 10 | issue = 11 | pages = 2952 | date = October 2021 | pmid = 34831175 | pmc = 8616336 | doi = 10.3390/cells10112952 | doi-access = free }}</ref>

Transposable elements that are transcribed into RNA, reverse-transcribed into DNA, then reintegrated into the genome are called [[retrotransposon]]s.<ref name=Wicker07 /> Just as tandem repeats are further subcategorized based on the length of the repeating sequence, there are many different types of retrotransposons. Long interspersed nuclear elements ([[Long interspersed nuclear element|LINEs]]) are typically 3–7 kilobases in length.<ref name=Kramerov11>{{cite journal | vauthors = Kramerov DA, Vassetzky NS | title = SINEs | journal = Wiley Interdisciplinary Reviews. RNA | volume = 2 | issue = 6 | pages = 772–786 | date = 2011 | pmid = 21976282 | doi = 10.1002/wrna.91 | s2cid = 222199613 }}</ref> Short interspersed nuclear elements ([[Short interspersed nuclear element|SINEs]]) are typically 100-300 base pairs and no longer than 600 base pairs.<ref name=Kramerov11 /> Long-terminal repeat retrotransposons (LTRs) are a third major class of retrotransposons and are characterized by highly repetitive sequences as the ends of the repeat.<ref name=Wicker07 /> When a transposable element does not proceed through RNA as an intermediate, it is called a [[DNA transposon]].<ref name=Wicker07 /> Other classification systems refer to retrotransposons as "Class I" and DNA transposons as "Class II" transposable elements.<ref name=Nicolau21 />

Transposable elements are estimated to constitute 45% of the human genome.<ref>{{cite journal | vauthors = Lee HE, Ayarpadikannan S, Kim HS | title = Role of transposable elements in genomic rearrangement, evolution, gene regulation and epigenetics in primates | journal = Genes & Genetic Systems | volume = 90 | issue = 5 | pages = 245–257 | date = 2015 | pmid = 26781081 | doi = 10.1266/ggs.15-00016 | doi-access = free }}</ref> Since uncontrolled propagation of TEs could wreak havoc on the genome, many regulatory mechanisms have evolved to silence their spread, including DNA methylation, histone modifications, non-coding RNAs (ncRNAs) including small interfering RNA (siRNA), chromatin remodelers, histone variants, and other epigenetic factors.<ref name=Nicolau21 /> However, TEs play a wide variety of important biological functions. When TEs are introduced into a new host, such as from a virus, they increase genetic diversity.<ref name=Nicolau21 /> In some cases, host organisms find new functions for the proteins which arise from expressing TEs in an evolutionary process called TE exaptation.<ref name=Nicolau21 /> Recent research also suggests that TEs serve to maintain higher-order chromatin structure and 3D genome organization.<ref>{{cite journal | vauthors = Mangiavacchi A, Liu P, Della Valle F, Orlando V | title = New insights into the functional role of retrotransposon dynamics in mammalian somatic cells | journal = Cellular and Molecular Life Sciences | volume = 78 | issue = 13 | pages = 5245–56 | date = July 2021 | pmid = 33990851 | pmc = 8257530 | doi = 10.1007/s00018-021-03851-5 }}</ref> Furthermore, TEs contribute to regulating the expression of other genes by serving as distal [[Enhancer (genetics)|enhancers]] and transcription factor binding sites.<ref>{{cite journal | vauthors = Ichiyanagi K | title = Epigenetic regulation of transcription and possible functions of mammalian short interspersed elements, SINEs | journal = Genes & Genetic Systems | volume = 88 | issue = 1 | pages = 19–29 | date = 2013 | pmid = 23676707 | doi = 10.1266/ggs.88.19 | doi-access = free }}</ref>

The prevalence of interspersed elements in the genome has garnered attention for more research on their origins and functions. Some specific interspersed elements have been characterized, such as the Alu repeat and LINE1.

===Intrachromosomal recombination===

[[Homologous recombination]] between chromosomal repeated sequences in somatic cells of ''[[Nicotiana tabacum]]'' was found to be increased by exposure to [[mitomycin C]], a bifunctional alkylating agent that [[crosslinking of DNA|crosslinks DNA]] strands.<ref name = Lebel1993>{{cite journal |vauthors=Lebel EG, Masson J, Bogucki A, Paszkowski J |title=Stress-induced intrachromosomal recombination in plant somatic cells |journal=Proc Natl Acad Sci U S A |volume=90 |issue=2 |pages=422–6 |date=January 1993 |pmid=11607349 |pmc=45674 |doi=10.1073/pnas.90.2.422 |doi-access=free |bibcode=1993PNAS...90..422L }}</ref>  This increase in recombination was attributed to increased intrachromosomal recombinational repair.<ref name = Lebel1993/>  By this process, mitomycin C damaged DNA in one sequence is repaired using intact information from the other repeated sequence.

=== Direct and inverted repeats ===
While tandem and interspersed repeats are distinguished based on their location in the genome, direct and inverted repeats are distinguished based on the ordering of the nucleotide bases. [[Direct repeat]]s occur when a nucleotide sequence is repeated with the same directionality. [[Inverted repeat]]s occur when a nucleotide sequence is repeated in the inverse direction. For example, a direct repeat of "CATCAT" would be another repetition of "CATCAT". In contrast, the inverted repeated would be "ATGATG". When there are no nucleotides separating the inverted repeat, such as "CATCATATGATG", the sequence is called a palindromic repeat. Inverted repeats can play structural roles in DNA and RNA by forming stem loops and cruciforms.<ref>{{cite journal | vauthors = Pearson CE, Zorbas H, Price GB, Zannis-Hadjopoulos M | title = Inverted repeats, stem-loops, and cruciforms: significance for initiation of DNA replication | journal = Journal of Cellular Biochemistry | volume = 63 | issue = 1 | pages = 1–22 | date = October 1996 | pmid = 8891900 | doi = 10.1002/(SICI)1097-4644(199610)63:1<1::AID-JCB1>3.0.CO;2-3 | s2cid = 22204780 | eissn = 1097-4644 }}</ref>