Thematische Bibliographien / Extrachromosomal circular DNA / Zeitschriftenartikel
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Zeitschriftenartikel zum Thema „Extrachromosomal circular DNA“

Autor: Grafiati
Veröffentlicht am 1. Juli 2021
Zuletzt aktualisiert am 1. Februar 2023

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1

Gonzalez, Rocio Chamorro, Thomas Conrad, Robin Xu, Madalina Giurgiu, Maja Cwikla, Katharina Kasack, Lotte Brückner et al. „Abstract 1693: Dissecting intercellular extrachromosomal circular DNA heterogeneity in single cancer cells with scEC&T-seq“. Cancer Research 82, Nr. 12_Supplement (15.06.2022): 1693. http://dx.doi.org/10.1158/1538-7445.am2022-1693.

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Abstract Extrachromosomal DNA circularization is a common event in cancer cells and frequently serves as a vehicle for cancer oncogene amplification. Random segregation of oncogene-containing extrachromosomal circular DNA promotes rapid intercellular heterogeneity, conferring tumors the ability to rapidly evolve and escape therapy. Smaller, copy-number neutral extrachromosomal circular DNAs are also abundantly identified in both healthy and malignant tissues, but their function in cancer is still unknown. Understanding how extrachromosomal circular DNAs contribute to intercellular heterogeneity in cancer cells remains crucial, however methods for an unbiased characterization of extrachromosomal circular DNAs in single cells are lacking. We introduce scEC&T-seq (single cell extrachromosomal circular DNA and transcriptomic sequencing), a method for parallel detection of extrachromosomal circular DNAs and full-length mRNA in single cells. We demonstrate the ability of our method to isolate and detect extrachromosomal circular DNAs genome-wide from all range of sizes in single cells. We observed that whereas large oncogene-containing circular DNAs are clonally present in most cancer cells, only a very small fraction of small circular DNAs are recurrently identified in single cells, indicating yet unknown prerequisites for maintenance and propagation. Our method was able to capture and recapitulate the structural complexity of oncogene-containing extrachromosomal circular DNAs in single cells, and the matching transcriptomic data allowed us to identify fusion transcripts resulting from the rearranged extrachromosomal structures. In addition, we observed that whereas the main structure of extrachromosomal circular DNAs is mostly stable in single cells, intercellular differences in extrachromosomal circular DNAs’ content can drive differences in oncogene transcription levels in single cells. We envision that by integrating extrachromosomal circular DNA and mRNA sequencing, our method will not only be useful to investigate the impact of intercellular heterogeneity in extrachromosomal circular DNA in tumor evolution, but also to interrogate its function in other biological and pathological processes. Citation Format: Rocio Chamorro Gonzalez, Thomas Conrad, Robin Xu, Madalina Giurgiu, Maja Cwikla, Katharina Kasack, Lotte Brückner, Eric van Leen, Elias Rodriguez-Fos, Konstantin Helmsauer, Heathcliff Dorado Garcia, Yi Bei, Karin Schmelz, Sascha Sauer, Angelika Eggert, Johannes H. Schulte, Roland F. Schwarz, Kerstin Haase, Richard P. Koche, Anton G. Henssen. Dissecting intercellular extrachromosomal circular DNA heterogeneity in single cancer cells with scEC&T-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1693.
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Wang, Keyi, Hui Tian, Lequn Wang, Lin Wang, Yacong Tan, Ziting Zhang, Kai Sun et al. „Deciphering extrachromosomal circular DNA in Arabidopsis“. Computational and Structural Biotechnology Journal 19 (2021): 1176–83. http://dx.doi.org/10.1016/j.csbj.2021.01.043.

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Shimizu, Noriaki. „Gene Amplification and the Extrachromosomal Circular DNA“. Genes 12, Nr. 10 (28.09.2021): 1533. http://dx.doi.org/10.3390/genes12101533.

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Oncogene amplification is closely linked to the pathogenesis of a broad spectrum of human malignant tumors. The amplified genes localize either to the extrachromosomal circular DNA, which has been referred to as cytogenetically visible double minutes (DMs), or submicroscopic episome, or to the chromosomal homogeneously staining region (HSR). The extrachromosomal circle from a chromosome arm can initiate gene amplification, resulting in the formation of DMs or HSR, if it had a sequence element required for replication initiation (the replication initiation region/matrix attachment region; the IR/MAR), under a genetic background that permits gene amplification. In this article, the nature, intracellular behavior, generation, and contribution to cancer genome plasticity of such extrachromosomal circles are summarized and discussed by reviewing recent articles on these topics. Such studies are critical in the understanding and treating human cancer, and also for the production of recombinant proteins such as biopharmaceuticals by increasing the recombinant genes in the cells.
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Cohen, Sarit, Sophie Menut und Marcel Méchali. „Regulated Formation of Extrachromosomal Circular DNA Molecules during Development in Xenopus laevis“. Molecular and Cellular Biology 19, Nr. 10 (01.10.1999): 6682–89. http://dx.doi.org/10.1128/mcb.19.10.6682.

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ABSTRACT Extrachromosomal circular DNA molecules of chromosomal origin have been detected in many organisms and are thought to reflect genomic plasticity in eukaryotic cells. Here we report a developmentally regulated formation of extrachromosomal circular DNA that occurs de novo in preblastula Xenopus embryos. This specific DNA population is not detected in the male or female germ cells and is dramatically reduced in later developmental stages and in adult tissues. The activity responsible for the de novo production of extrachromosomal circles is maternally inherited, is stored in the unfertilized egg, and requires genomic DNA as a template. The formation of circular molecules does not require genomic DNA replication but both processes can occur simultaneously in the early development. The production of extrachromosomal circular DNA does not proceed at random since multimers of the tandemly repeated sequence satellite 1 were over-represented in the circle population, while other sequences (such as ribosomal DNA and JCC31 repeated sequence) were not detected. This phenomenon reveals an unexpected plasticity of the embryonic genome which is restricted to the early developmental stage.
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Møller, Henrik D., Lance Parsons, Tue S. Jørgensen, David Botstein und Birgitte Regenberg. „Extrachromosomal circular DNA is common in yeast“. Proceedings of the National Academy of Sciences 112, Nr. 24 (02.06.2015): E3114—E3122. http://dx.doi.org/10.1073/pnas.1508825112.

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Examples of extrachromosomal circular DNAs (eccDNAs) are found in many organisms, but their impact on genetic variation at the genome scale has not been investigated. We mapped 1,756 eccDNAs in the Saccharomyces cerevisiae genome using Circle-Seq, a highly sensitive eccDNA purification method. Yeast eccDNAs ranged from an arbitrary lower limit of 1 kb up to 38 kb and covered 23% of the genome, representing thousands of genes. EccDNA arose both from genomic regions with repetitive sequences ≥15 bases long and from regions with short or no repetitive sequences. Some eccDNAs were identified in several yeast populations. These eccDNAs contained ribosomal genes, transposon remnants, and tandemly repeated genes (HXT6/7, ENA1/2/5, and CUP1-1/-2) that were generally enriched on eccDNAs. EccDNAs seemed to be replicated and 80% contained consensus sequences for autonomous replication origins that could explain their maintenance. Our data suggest that eccDNAs are common in S. cerevisiae, where they might contribute substantially to genetic variation and evolution.
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Sun, Teng, Kun Wang, Cuiyun Liu, Yin Wang, Jianxun Wang und Peifeng Li. „Identification of Extrachromosomal Linear microDNAs Interacted with microRNAs in the Cell Nuclei“. Cells 8, Nr. 2 (01.02.2019): 111. http://dx.doi.org/10.3390/cells8020111.

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Extrachromosomal DNA exists in two forms: Covalently closed circular and linear. While diverse types of circular extrachromosomal DNA have been identified with validated in vivo functions, little is known about linear extrachromosomal DNA. In this study, we identified small, single-stranded linear extrachromosomal DNAs (SSLmicroDNAs) in the nuclei of mouse hearts, mouse brains, HEK293, and HeLa cells. We used a pull-down system based on the single-stranded DNA binding protein RecAf. We found that SSLmicroDNAs aligned predominantly to intergenic and intragenic regions of the genome, owned a variety of single nucleotide polymorphism sites, and strongly associated with H3K27Ac marks. The regions were tens to hundreds of nucleotides long, periodically separated by AT, TT, or AA dinucleotides. It has been demonstrated that SSLmicroDNAs in the nuclei of normal cells target microRNAs, which regulate biological processes. In summary, our present work identified a new form of extrachromosomal DNAs, which function inside nuclei and interact with microRNAs. This finding provides a possible research field into the function of extrachromosomal DNA.
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Yerlici, V. Talya, Michael W. Lu, Carla R. Hoge, Richard V. Miller, Rafik Neme, Jaspreet S. Khurana, John R. Bracht und Laura F. Landweber. „Programmed genome rearrangements in Oxytricha produce transcriptionally active extrachromosomal circular DNA“. Nucleic Acids Research 47, Nr. 18 (28.08.2019): 9741–60. http://dx.doi.org/10.1093/nar/gkz725.

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Abstract Extrachromosomal circular DNA (eccDNA) is both a driver of eukaryotic genome instability and a product of programmed genome rearrangements, but its extent had not been surveyed in Oxytricha, a ciliate with elaborate DNA elimination and translocation during development. Here, we captured rearrangement-specific circular DNA molecules across the genome to gain insight into its processes of programmed genome rearrangement. We recovered thousands of circularly excised Tc1/mariner-type transposable elements and high confidence non-repetitive germline-limited loci. We verified their bona fide circular topology using circular DNA deep-sequencing, 2D gel electrophoresis and inverse polymerase chain reaction. In contrast to the precise circular excision of transposable elements, we report widespread heterogeneity in the circular excision of non-repetitive germline-limited loci. We also demonstrate that circular DNAs are transcribed in Oxytricha, producing rearrangement-specific long non-coding RNAs. The programmed formation of thousands of eccDNA molecules makes Oxytricha a model system for studying nucleic acid topology. It also suggests involvement of eccDNA in programmed genome rearrangement.
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Clark, C. G., und G. A. Cross. „rRNA genes of Naegleria gruberi are carried exclusively on a 14-kilobase-pair plasmid“. Molecular and Cellular Biology 7, Nr. 9 (September 1987): 3027–31. http://dx.doi.org/10.1128/mcb.7.9.3027-3031.1987.

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An extrachromosomal DNA was discovered in Naegleria gruberi. The 3,000 to 5,000 copies per cell of this 14-kilobase-pair circular plasmid carry all the 18S, 28S, and 5.8S rRNA genes. The presence of the ribosomal DNA of an organism exclusively on a circular extrachromosomal element is without precedent, and Naegleria is only the third eucaryotic genus in which a nuclear plasmid DNA has been found.
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Clark, C. G., und G. A. Cross. „rRNA genes of Naegleria gruberi are carried exclusively on a 14-kilobase-pair plasmid.“ Molecular and Cellular Biology 7, Nr. 9 (September 1987): 3027–31. http://dx.doi.org/10.1128/mcb.7.9.3027.

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An extrachromosomal DNA was discovered in Naegleria gruberi. The 3,000 to 5,000 copies per cell of this 14-kilobase-pair circular plasmid carry all the 18S, 28S, and 5.8S rRNA genes. The presence of the ribosomal DNA of an organism exclusively on a circular extrachromosomal element is without precedent, and Naegleria is only the third eucaryotic genus in which a nuclear plasmid DNA has been found.
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Ain, Quratul, Christian Schmeer, Diane Wengerodt, Otto W. Witte und Alexandra Kretz. „Extrachromosomal Circular DNA: Current Knowledge and Implications for CNS Aging and Neurodegeneration“. International Journal of Molecular Sciences 21, Nr. 7 (02.04.2020): 2477. http://dx.doi.org/10.3390/ijms21072477.

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Still unresolved is the question of how a lifetime accumulation of somatic gene copy number alterations impact organ functionality and aging and age-related pathologies. Such an issue appears particularly relevant in the broadly post-mitotic central nervous system (CNS), where non-replicative neurons are restricted in DNA-repair choices and are prone to accumulate DNA damage, as they remain unreplaced over a lifetime. Both DNA injuries and consecutive DNA-repair strategies are processes that can evoke extrachromosomal circular DNA species, apparently from either part of the genome. Due to their capacity to amplify gene copies and related transcripts, the individual cellular load of extrachromosomal circular DNAs will contribute to a dynamic pool of additional coding and regulatory chromatin elements. Analogous to tumor tissues, where the mosaicism of circular DNAs plays a well-characterized role in oncogene plasticity and drug resistance, we suggest involvement of the “circulome” also in the CNS. Accordingly, we summarize current knowledge on the molecular biogenesis, homeostasis and gene regulatory impacts of circular extrachromosomal DNA and propose, in light of recent discoveries, a critical role in CNS aging and neurodegeneration. Future studies will elucidate the influence of individual extrachromosomal DNA species according to their sequence complexity and regional distribution or cell-type-specific abundance.
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Darby, A. C., J. Lagnel, C. Z. Matthew, K. Bourtzis, I. Maudlin und S. C. Welburn. „Extrachromosomal DNA of the Symbiont Sodalis glossinidius“. Journal of Bacteriology 187, Nr. 14 (Juli 2005): 5003–7. http://dx.doi.org/10.1128/jb.187.14.5003-5007.2005.

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ABSTRACT The extrachromosomal DNA of Sodalis glossinidius from two tsetse fly species was sequenced and contained four circular elements: three plasmids, pSG1 (82 kb), pSG2 (27 kb), and pSG4 (11 kb), and a bacteriophage-like pSG3 (19 kb) element. The information suggests S. glossinidius is evolving towards an obligate association with tsetse flies.
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Diaz-Lara, Alfredo, David H. Gent und Robert R. Martin. „Identification of Extrachromosomal Circular DNA in Hop via Rolling Circle Amplification“. Cytogenetic and Genome Research 148, Nr. 2-3 (2016): 237–40. http://dx.doi.org/10.1159/000445849.

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During a survey for new viruses affecting hop plants, a circular DNA molecule was identified via rolling circle amplification (RCA) and later characterized. A small region of the 5.7-kb long molecule aligned with a microsatellite region in the Humulus lupulus genome, and no coding sequence was identified. Sequence analysis and literature review suggest that the small DNA molecule is an extranuclear DNA element, specifically, an extrachromosomal circular DNA (eccDNA), and its presence was confirmed by electron microscopy. This work is the first report of eccDNAs in the family Cannabaceae. Additionally, this work highlights the advantages of using RCA to study extrachromosomal DNA in higher plants.
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Mehta, Devang, Luc Cornet, Matthias Hirsch-Hoffmann, Syed Shan-e.-Ali Zaidi und Hervé Vanderschuren. „Full-length sequencing of circular DNA viruses and extrachromosomal circular DNA using CIDER-Seq“. Nature Protocols 15, Nr. 5 (03.04.2020): 1673–89. http://dx.doi.org/10.1038/s41596-020-0301-0.

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Wilson, R. J., und D. H. Williamson. „Extrachromosomal DNA in the Apicomplexa“. Microbiology and Molecular Biology Reviews 61, Nr. 1 (März 1997): 1–16. http://dx.doi.org/10.1128/mmbr.61.1.1-16.1997.

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Malaria and related apicomplexan parasites have two highly conserved organellar genomes: one is of plastid (pl) origin, and the other is mitochondrial (mt). The organization of both organellar DNA molecules from the human malaria parasite Plasmodium falciparum has been determined, and they have been shown to be tightly packed with genes. The 35-kb circular DNA is the smallest known vestigial plastid genome and is presumed to be functional. All but two of its recognized genes are involved with genetic expression: one of the two encodes a member of the clp family of molecular chaperones, and the other encodes a conserved protein of unknown function found both in algal plastids and in eubacterial genomes. The possible evolutionary source and intracellular location of the plDNA are discussed. The 6-kb tandemly repeated mt genome is the smallest known and codes for only three proteins (cytochrome b and two subunits of cytochrome oxidase) as well as two bizarrely fragmented rRNAs. The organization of the mt genome differs somewhat among genera. The mtDNA sequence provides information not otherwise available about the structure of apicomplexan cytochrome b as well as the unusually fragmented rRNAs. The malarial mtDNA has a phage-like replication mechanism and undergoes extensive recombination like the mtDNA of some other lower eukaryotes.
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Wu, Sihan, Vineet Bafna, Howard Y. Chang und Paul S. Mischel. „Extrachromosomal DNA: An Emerging Hallmark in Human Cancer“. Annual Review of Pathology: Mechanisms of Disease 17, Nr. 1 (24.01.2022): 367–86. http://dx.doi.org/10.1146/annurev-pathmechdis-051821-114223.

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Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution.
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Hull, Ryan M., und Jonathan Houseley. „The adaptive potential of circular DNA accumulation in ageing cells“. Current Genetics 66, Nr. 5 (15.04.2020): 889–94. http://dx.doi.org/10.1007/s00294-020-01069-9.

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Abstract Carefully maintained and precisely inherited chromosomal DNA provides long-term genetic stability, but eukaryotic cells facing environmental challenges can benefit from the accumulation of less stable DNA species. Circular DNA molecules lacking centromeres segregate randomly or asymmetrically during cell division, following non-Mendelian inheritance patterns that result in high copy number instability and massive heterogeneity across populations. Such circular DNA species, variously known as extrachromosomal circular DNA (eccDNA), microDNA, double minutes or extrachromosomal DNA (ecDNA), are becoming recognised as a major source of the genetic variation exploited by cancer cells and pathogenic eukaryotes to acquire drug resistance. In budding yeast, circular DNA molecules derived from the ribosomal DNA (ERCs) have been long known to accumulate with age, but it is now clear that aged yeast also accumulate other high-copy protein-coding circular DNAs acquired through both random and environmentally-stimulated recombination processes. Here, we argue that accumulation of circular DNA provides a reservoir of heterogeneous genetic material that can allow rapid adaptation of aged cells to environmental insults, but avoids the negative fitness impacts on normal growth of unsolicited gene amplification in the young population.
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Renault, S., F. Degroote und G. Picard. „Identification of short tandemly repeated sequences in extrachromosomal circular DNAs from Drosophila melanogaster embryos“. Genome 36, Nr. 2 (01.04.1993): 244–54. http://dx.doi.org/10.1139/g93-034.

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A sequence (scl) belonging to the recently identified dodeca satellite family was found to be a major family of extrachromosomal circular DNA molecules from Drosophila melanogaster embryos. The basic unit consists of the 11-bp repeat 5′ ACTGGTCCCGT 3′, is 63% G + C rich, and shares some similarity with the Escherichia coli chi sequence. This family accounts for only about 0.06% of the genome but very likely for a higher proportion of the circular DNA molecules. It is organized in the genome into at least five main clusters contained in DNA fragments larger than 20 kb and several minor clusters. These clusters are located in the heterochromatic pericentromeric regions. Two other families of simple repeated sequences, the 1.686 g/cm3 (5′ AATAACATAG 3′) and the 1.705 g/cm3 (5′ AAGAG 3′) satellite DNAs, were also found in circular DNAs, while another family, the 1.672 g/cm3 (5′ AATAT 3′), was not detected. The representation of the simple repeated sequences in circular molecules is not correlated to their genomic representation. Among the seven families of sequences identified to date in extrachromosomal circular DNAs from embryos, the dodeca satellite, the 240-bp repeat of the rDNA intergenic spacer, and the 1.688 and 1.705 g/cm3 satellite DNAs are the most represented families, while the 5S genes, the histone genes, and the 1.686 g/cm3 satellite DNA are present in a lower amount.Key words: D. melanogaster, extrachromosomal circular DNAs, repeated sequences, satellite DNA.
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Koche, Richard P., Elias Rodriguez-Fos, Konstantin Helmsauer, Martin Burkert, Ian C. MacArthur, Jesper Maag, Rocio Chamorro et al. „Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma“. Nature Genetics 52, Nr. 1 (16.12.2019): 29–34. http://dx.doi.org/10.1038/s41588-019-0547-z.

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Cohen, S., und S. Lavi. „Induction of circles of heterogeneous sizes in carcinogen-treated cells: two-dimensional gel analysis of circular DNA molecules.“ Molecular and Cellular Biology 16, Nr. 5 (Mai 1996): 2002–14. http://dx.doi.org/10.1128/mcb.16.5.2002.

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Extrachromosomal circular DNA molecules are associated with genomic instability, and circles containing inverted repeats were suggested to be the early amplification products. Here we present for the first time the use of neutral-neutral two-dimensional (2D) gel electrophoresis as a technique for the identification, isolation, and characterization of heterogeneous populations of circular molecules. Using this technique, we demonstrated that in N-methyl-N'-nitro-N-nitrosoguanidine-treated simian virus 40-transformed Chinese hamster cells (CO60 cells), the viral sequences are amplified as circular molecules of various sizes. The supercoiled circular fraction was isolated and was shown to contain molecules with inverted repeats. 2D gel analysis of extrachromosomal DNA from CHO cells revealed circular molecules containing highly repetitive DNA which are similar in size to the simian virus 40-amplified molecules. Moreover, enhancement of the amount of circular DNA was observed upon N-methyl-N'-nitro-N-nitrosoguanidine treatment of CHO cells. The implications of these findings regarding the processes of gene amplification and genomic instability and the possible use of the 2D gel technique to study these phenomena are discussed.
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Mischel, Paul S. „Abstract SY03-02: Extrachromosomal DNA (ecDNA): Cancer's dynamic circular genome“. Cancer Research 82, Nr. 12_Supplement (15.06.2022): SY03–02—SY03–02. http://dx.doi.org/10.1158/1538-7445.am2022-sy03-02.

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Abstract Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA poses one of the greatest challenges for cancer patients, affecting children and adults and women and men, with a wide variety of cancer types. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. ecDNA, because of its non-chromosomal inheritance, drives high-copy number oncogene amplification and enables tumors to evolve their genomes rapidly, contributing to treatment resistance and shorter survival for patients. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription. In this talk, I will discuss recent collaborative discoveries that highlight how the higher order, spatial organization of ecDNA, and its mechanism of inheritance, contributes to aggressive tumorigenesis, accelerated evolution, and treatment resistance. Citation Format: Paul S. Mischel. Extrachromosomal DNA (ecDNA): Cancer's dynamic circular genome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY03-02.
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Peng, Haoran, Marie Mirouze und Etienne Bucher. „Extrachromosomal circular DNA: A neglected nucleic acid molecule in plants“. Current Opinion in Plant Biology 69 (Oktober 2022): 102263. http://dx.doi.org/10.1016/j.pbi.2022.102263.

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Sin, Sarah T. K., Peiyong Jiang, Jiaen Deng, Lu Ji, Suk Hang Cheng, Anindya Dutta, Tak Y. Leung, K. C. Allen Chan, Rossa W. K. Chiu und Y. M. Dennis Lo. „Identification and characterization of extrachromosomal circular DNA in maternal plasma“. Proceedings of the National Academy of Sciences 117, Nr. 3 (03.01.2020): 1658–65. http://dx.doi.org/10.1073/pnas.1914949117.

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We explored the presence of extrachromosomal circular DNA (eccDNA) in the plasma of pregnant women. Through sequencing following either restriction enzyme or Tn5 transposase treatment, we identified eccDNA molecules in the plasma of pregnant women. These eccDNA molecules showed bimodal size distributions peaking at ∼202 and ∼338 bp with distinct 10-bp periodicity observed throughout the size ranges within both peaks, suggestive of their nucleosomal origin. Also, the predominance of the 338-bp peak of eccDNA indicated that eccDNA had a larger size distribution than linear DNA in human plasma. Moreover, eccDNA of fetal origin were shorter than the maternal eccDNA. Genomic annotation of the overall population of eccDNA molecules revealed a preference of these molecules to be generated from 5′-untranslated regions (5′-UTRs), exonic regions, and CpG island regions. Two sets of trinucleotide repeat motifs flanking the junctional sites of eccDNA supported multiple possible models for eccDNA generation. This work highlights the topologic analysis of plasma DNA, which is an emerging direction for circulating nucleic acid research and applications.
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Navrátilová, Alice, Andrea Koblížková und Jiří Macas. „Survey of extrachromosomal circular DNA derived from plant satellite repeats“. BMC Plant Biology 8, Nr. 1 (2008): 90. http://dx.doi.org/10.1186/1471-2229-8-90.

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Fujimoto, S., T. Tsuda, M. Toda und H. Yamagishi. „Transposon-like sequences in extrachromosomal circular DNA from mouse thymocytes.“ Proceedings of the National Academy of Sciences 82, Nr. 7 (01.04.1985): 2072–76. http://dx.doi.org/10.1073/pnas.82.7.2072.

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Chiu, Rossa W. K., Anindya Dutta, Anton G. Henssen, Y. M. Dennis Lo, Paul Mischel und Birgitte Regenberg. „What Is Extrachromosomal Circular DNA and What Does It Do?“ Clinical Chemistry 66, Nr. 6 (29.05.2020): 754–59. http://dx.doi.org/10.1093/clinchem/hvaa096.

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Cohen, S. „Extrachromosomal Circular DNA of Tandemly Repeated Genomic Sequences in Drosophila“. Genome Research 13, Nr. 6 (12.05.2003): 1133–45. http://dx.doi.org/10.1101/gr.907603.

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Khan, Safir Ullah, und Munir Ullah Khan. „Extra Chromosomal Circular DNA: Recent Advances in Research“. Journal of Biomedical Research & Environmental Sciences 3, Nr. 4 (April 2022): 445–52. http://dx.doi.org/10.37871/jbres1463.

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Extrachromosomal circular DNA (eccDNA) is a circular DNA molecule outside of eukaryotic staining, in which DNA forms in the genome or exogenous DNA in the cell. eccDNA is a special class of genetic material that can carry complete genes encoding functional proteins or RNA. Studies have shown that eccDNA can participate in various physiological and pathological processes in a special way, such as aging and the occurrence of tumors. This paper reviews the latest research progress of eccDNA and further expounds on the relationship between eccDNA and tumors.
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Reinhard H. Dennin. „Fundamentals of extrachromosomal circular DNA in human cells - Genetic activities as regards cancer promotion alongside chromosomal DNA“. World Journal of Advanced Research and Reviews 8, Nr. 2 (30.11.2020): 279–84. http://dx.doi.org/10.30574/wjarr.2020.8.2.0442.

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In addition to chromosomal DNA (chr-DNA) and mitochondrial DNA, eukaryotic cells contain extrachromosomal DNA (ec-DNA). Analysed extrachromosomal circular DNA (ecc-DNA) accounts for up to 20% of the total cellular DNA. Ecc-DNAs contain coding and non-coding sequences originating from chr-DNA and mobile genetic elements (MGEs). MGEs include sequences such as transposons, which have the potential to move between different and the same DNA molecules, thereby, for example, causing rearrangements and inactivation of genes. Ecc DNAs have aroused interest in diseases such as malignancies and diagnostic procedures relating to this. A database to collect ecc-DNA has been established. Investigations are needed to find possible differences in sequences of chr-DNA after sequencing the whole cellular DNA (WCD), namely: chr-DNA plus ec-/ecc-DNA compared to chr-DNA, which is separated from ec-/ecc-DNA. Standards for sequencing protocols of WCD have to be developed that also reveal the sequences of ecc-DNA; this concerns “single-cell genomics” in particular.
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Liao, Zhenyu, Wang Jiang, Longyun Ye, Tianjiao Li, Xianjun Yu und Liang Liu. „Classification of extrachromosomal circular DNA with a focus on the role of extrachromosomal DNA (ecDNA) in tumor heterogeneity and progression“. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1874, Nr. 1 (August 2020): 188392. http://dx.doi.org/10.1016/j.bbcan.2020.188392.

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Krikau, M. F., und C. L. Jahn. „Tec2, a second transposon-like element demonstrating developmentally programmed excision in Euplotes crassus“. Molecular and Cellular Biology 11, Nr. 9 (September 1991): 4751–59. http://dx.doi.org/10.1128/mcb.11.9.4751-4759.1991.

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The analysis of a repetitive DNA interruption of the micronuclear precursor to a 0.85-kb macronuclear gene in the hypotrich Euplotes crassus has led to the identification of a second transposon-like element named Tec2. Two copies of this element, one inserted into the other, compose the interruption. The Tec2 element resembles the previously characterized Tec1 element in overall size, copy number, length, and extreme terminal sequence of its inverted repeats and in the apparent use of a 5'-TA-3' target site. In addition, extrachromosomal circular forms of Tec2 appear in DNA isolated from cells undergoing macronuclear development at the same time and with the same conformation as extrachromosomal circular forms of Tec1. These similarities suggest that the Tec1 and Tec2 elements may be under the same type of regulation during macronuclear development.
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Krikau, M. F., und C. L. Jahn. „Tec2, a second transposon-like element demonstrating developmentally programmed excision in Euplotes crassus.“ Molecular and Cellular Biology 11, Nr. 9 (September 1991): 4751–59. http://dx.doi.org/10.1128/mcb.11.9.4751.

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The analysis of a repetitive DNA interruption of the micronuclear precursor to a 0.85-kb macronuclear gene in the hypotrich Euplotes crassus has led to the identification of a second transposon-like element named Tec2. Two copies of this element, one inserted into the other, compose the interruption. The Tec2 element resembles the previously characterized Tec1 element in overall size, copy number, length, and extreme terminal sequence of its inverted repeats and in the apparent use of a 5'-TA-3' target site. In addition, extrachromosomal circular forms of Tec2 appear in DNA isolated from cells undergoing macronuclear development at the same time and with the same conformation as extrachromosomal circular forms of Tec1. These similarities suggest that the Tec1 and Tec2 elements may be under the same type of regulation during macronuclear development.
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32

Mullican, John C., Nora M. Chapman und Steven Tracy. „Complete Genome Sequence of the Circular Extrachromosomal Element of Naegleria gruberi Strain EGB Ribosomal DNA“. Genome Announcements 6, Nr. 6 (08.02.2018): e00020-18. http://dx.doi.org/10.1128/genomea.00020-18.

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ABSTRACT The circular extrachromosomal element of Naegleria gruberi strain EGB was linearized, molecularly cloned, and fully sequenced. The sequence comprises 14,007 bp and encodes the organism’s rRNA genes, two potential open reading frames, and numerous repeated sequence regions.
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Prada-Luengo, Iñigo, Henrik D. Møller, Rasmus A. Henriksen, Qian Gao, Camilla Eggert Larsen, Sefa Alizadeh, Lasse Maretty, Jonathan Houseley und Birgitte Regenberg. „Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae“. Nucleic Acids Research 48, Nr. 14 (01.07.2020): 7883–98. http://dx.doi.org/10.1093/nar/gkaa545.

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Abstract Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y’ regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.
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Chapman, Owen, Jens Luebeck, Shanqing Wang, Alexandra Garancher, Jon Larson, Joshua Lange, Ivy Tsz Lo Wong et al. „OMIC-01. THE LANDSCAPE OF EXTRACHROMOSOMAL CIRCULAR DNA IN MEDULLOBLASTOMA SUBGROUPS“. Neuro-Oncology 23, Supplement_1 (01.06.2021): i37. http://dx.doi.org/10.1093/neuonc/noab090.148.

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Abstract Extrachromosomal circular DNA (ecDNA) is an important driver of particularly aggressive human cancers. However, the prevalence of ecDNA, and its role in tumor development and progression in the different molecular subgroups of medulloblastoma (MB), remain unknown. To answer these questions, we have assembled a multi-institutional retrospective cohort of 472 MB patients with available whole genome sequencing (WGS) data, drawing from three cancer genomic data repositories and covering all MB subgroups (WNT, SHH, Group 3 and Group 4). Using recent computational methods to detect and reconstruct ecDNA, we find ecDNA in 66 patients (14%) and observe that the presence of ecDNA is associated with significantly poorer outcomes. By subgroup, ecDNA was found in 0/24 WNT (0%), 22/109 SHH (20%), 15/107 Group 3 (14%) and 20/181 Group 4 (11%) patients. Affected genomic loci harbor up to hundredfold amplification of oncogenes including MYC, MYCN, TERT, and other novel putative oncogenes. We further analyzed 24 patient-derived xenograft (PDX) and four cell line models of MB tumors. ecDNA was substantially more frequent in patient-derived models (17 of 29, 59%) than in our patient cohort. To elucidate the functional regulatory landscapes of ecDNAs in MB, we generated transcriptional (RNA-seq), accessible chromatin (ATAC-seq), and chromatin interaction (Hi-C) profiles of 6 MB tumor samples. In each case, we identify regulatory interactions that cross fusion breakpoints on the ecDNA, representing potential “enhancer rewiring” events which may contribute to transcriptional activation of co-amplified oncogenes. To test this hypothesis, we are currently conducting in-vitro CRISPRi screens targeting regulatory regions on the ecDNA of a MB cell line to determine whether these enhancers promote proliferation. In summary, our study analyzes the frequency, diversity and functional relevance of ecDNA across MB subgroups and provides strong justification for continued mechanistic studies of ecDNA in MB with the potential to uncover new therapeutic approaches.
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van Loon, Nanette, Douglas Miller und John P. Murnane. „Formation of extrachromosomal circular DNA in HeLa cells by nonhomologous recombination“. Nucleic Acids Research 22, Nr. 13 (1994): 2447–52. http://dx.doi.org/10.1093/nar/22.13.2447.

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36

Cohen, Sarit, Andreas Houben und Daniel Segal. „Extrachromosomal circular DNA derived from tandemly repeated genomic sequences in plants“. Plant Journal 53, Nr. 6 (15.12.2007): 1027–34. http://dx.doi.org/10.1111/j.1365-313x.2007.03394.x.

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37

Stanfield, Sharon W., und Donald R. Helinski. „Multiple mechanisms generate extrachromosomal circular DNA in Chinese hamster ovary cells“. Nucleic Acids Research 14, Nr. 8 (1986): 3527–38. http://dx.doi.org/10.1093/nar/14.8.3527.

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Koche, Richard P., Elias Rodriguez-Fos, Konstantin Helmsauer, Martin Burkert, Ian C. MacArthur, Jesper Maag, Rocio Chamorro et al. „Publisher Correction: Extrachromosomal circular DNA drives oncogenic genome remodeling in neuroblastoma“. Nature Genetics 52, Nr. 4 (27.02.2020): 464. http://dx.doi.org/10.1038/s41588-020-0598-1.

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39

Noto, Tomoko, Kazumori Yazaki und Hiroshi Endoh. „Developmentally regulated extrachromosomal circular DNA formation in the mesozoan Dicyema japonicum“. Chromosoma 111, Nr. 6 (März 2003): 359–68. http://dx.doi.org/10.1007/s00412-002-0216-2.

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40

Chang, Howard Y. „Abstract IA018: Reading and writing extrachromosomal DNA“. Cancer Research 82, Nr. 23_Supplement_2 (01.12.2022): IA018. http://dx.doi.org/10.1158/1538-7445.cancepi22-ia018.

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Abstract Cancer patients face an extraordinary challenge when oncogenes unleash themselves from chromosomes. Extrachromosomal DNA (ecDNA) are large, megabase-sized circular episomes containing oncogenes and regulatory DNA elements. EcDNAs have a remarkable transcriptional advantage and rapidly change copy number–a moving target driving accelerated evolution in cancer. We present a method for targeted purification of megabase-sized ecDNA by combining in-vitro CRISPR-Cas9 treatment and pulsed field gel electrophoresis of agarose-entrapped genomic DNA (CRISPR-CATCH). Targeted purification of ecDNA versus chromosomal DNA enabled phasing of genetic variants and provided definitive proof of oncogenic mutations exclusively on ecDNAs, discovery of ecDNA-specific demethylation with single molecule resolution, and accurate reconstruction of megabase- sized ecDNA structures with base-pair resolution. We model and test the impact of non-chromosomal oncogene inheritance—random identity by descent—on ecDNA on variation and selection. Integrating mathematical modeling, unbiased image analysis, CRISPR-based ecDNA generation, and live-cell imaging, we identify a set of basic “rules” for how random ecDNA inheritance drives oncogene copy number and distribution, resulting in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted cancer treatment. These new tool kits for reading and writing ecDNAs promise to unravel the genetic and epigenetic landscapes of ecDNA biogenesis, dynamics, and function. Citation Format: Howard Y. Chang. Reading and writing extrachromosomal DNA. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr IA018.
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Tatman, Philip D., und Joshua C. Black. „Extrachromosomal Circular DNA from TCGA Tumors Is Generated from Common Genomic Loci, Is Characterized by Self-Homology and DNA Motifs near Circle Breakpoints“. Cancers 14, Nr. 9 (06.05.2022): 2310. http://dx.doi.org/10.3390/cancers14092310.

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Extrachromosomal circular DNA has emerged as a frequent genomic alteration in tumors. High numbers of circular DNAs correspond to poor prognosis suggesting an important function in tumor biology. However, despite mounting evidence supporting the importance of circular DNA, little is known about their production, maintenance, or selection. To provide insight into these processes, we analyzed circular DNA elements computationally identified in 355 TCGA tumors spanning 22 tumor types. Circular DNAs originated from common genomic loci irrespective of cancer type. Genes found in circularized genomic regions were more likely to be expressed and were enriched in cancer-related pathways. Finally, in support of a model for circle generation through either a homology or microhomology-mediated process, circles exhibit homology near their breakpoint. These breakpoints are also enriched in specific DNA motifs. Our analysis supports a model where gene-containing circles emerge from common, highly transcribed regions through a homology-mediated process.
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42

Cohen, Zoya, und Sara Lavi. „Replication Independent Formation of Extrachromosomal Circular DNA in Mammalian Cell-Free System“. PLoS ONE 4, Nr. 7 (01.07.2009): e6126. http://dx.doi.org/10.1371/journal.pone.0006126.

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43

Chaudhuri, Gautam, und K. P. Chang. „A simple method for isolation of extrachromosomal circular DNA in unicellular eukaryotes“. Nucleic Acids Research 16, Nr. 5 (1988): 2341. http://dx.doi.org/10.1093/nar/16.5.2341.

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44

Kumar, Pankaj, Laura W. Dillon, Yoshiyuki Shibata, Amir A. Jazaeri, David R. Jones und Anindya Dutta. „Normal and Cancerous Tissues Release Extrachromosomal Circular DNA (eccDNA) into the Circulation“. Molecular Cancer Research 15, Nr. 9 (26.05.2017): 1197–205. http://dx.doi.org/10.1158/1541-7786.mcr-17-0095.

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45

Schoenlein, P. V., D. W. Shen, J. T. Barrett, I. Pastan und M. M. Gottesman. „Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicine-selected KB carcinoma cells.“ Molecular Biology of the Cell 3, Nr. 5 (Mai 1992): 507–20. http://dx.doi.org/10.1091/mbc.3.5.507.

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This study characterizes amplified structures carrying the human multidrug resistance (MDR) genes in colchicine-selected multidrug resistant KB cell lines and strongly supports a model of gene amplification in which small circular extrachromosomal DNA elements generated from contiguous chromosomal DNA regions multimerize to form cytologically detectable double minute chromosomes (DMs). The human MDR1 gene encodes the 170-kDa P-glycoprotein, which is a plasma membrane pump for many structurally unrelated chemotherapeutic drugs. MDR1 and its homolog, MDR2, undergo amplification when KB cells are subjected to stepwise selection in increasing concentrations of colchicine. The structure of the amplification unit at each step of drug selection was characterized using both high-voltage gel electrophoresis and pulsed-field gel electrophoresis (PFGE) techniques. An 890-kb submicroscopic extrachromosomal circular DNA element carrying the MDR1 and MDR2 genes was detected in cell line KB-ChR-8-5-11, the earliest step in drug selection in which conventional Southern/hybridization analyses detected MDR gene amplification. When KB-ChR-8-5-11 was subjected to stepwise increases in colchicine, this circular DNA element dimerized as detected by PFGE with and without digestion with Not 1, which linearizes the 890-kb amplicon. This dimerization process, which also occurred at the next step of colchicine selection, resulted in the formation of cytologically detectable DMs revealed by analysis of Giemsa-stained metaphase spreads.
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Koo, Dal-Hoe, William T. Molin, Christopher A. Saski, Jiming Jiang, Karthik Putta, Mithila Jugulam, Bernd Friebe und Bikram S. Gill. „Extrachromosomal circular DNA-based amplification and transmission of herbicide resistance in crop weedAmaranthus palmeri“. Proceedings of the National Academy of Sciences 115, Nr. 13 (12.03.2018): 3332–37. http://dx.doi.org/10.1073/pnas.1719354115.

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Gene amplification has been observed in many bacteria and eukaryotes as a response to various selective pressures, such as antibiotics, cytotoxic drugs, pesticides, herbicides, and other stressful environmental conditions. An increase in gene copy number is often found as extrachromosomal elements that usually contain autonomously replicating extrachromosomal circular DNA molecules (eccDNAs).Amaranthus palmeri, a crop weed, can develop herbicide resistance to glyphosate [N-(phosphonomethyl) glycine] by amplification of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, the molecular target of glyphosate. However, biological questions regarding the source of the amplifiedEPSPS, the nature of the amplified DNA structures, and mechanisms responsible for maintaining this gene amplification in cells and their inheritance remain unknown. Here, we report that amplifiedEPSPScopies in glyphosate-resistant (GR)A. palmeriare present in the form of eccDNAs with various conformations. The eccDNAs are transmitted during cell division in mitosis and meiosis to the soma and germ cells and the progeny by an as yet unknown mechanism of tethering to mitotic and meiotic chromosomes. We propose that eccDNAs are one of the components of McClintock’s postulated innate systems [McClintock B (1978)Stadler Genetics Symposium] that can rapidly produce soma variation, amplifyEPSPSgenes in the sporophyte that are transmitted to germ cells, and modulate rapid glyphosate resistance through genome plasticity and adaptive evolution.
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Kumar, Pankaj, Shashi Kiran, Shekhar Saha, Zhangli Su, Teressa Paulsen, Ajay Chatrath, Yoshiyuki Shibata, Etsuko Shibata und Anindya Dutta. „ATAC-seq identifies thousands of extrachromosomal circular DNA in cancer and cell lines“. Science Advances 6, Nr. 20 (Mai 2020): eaba2489. http://dx.doi.org/10.1126/sciadv.aba2489.

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Extrachromosomal circular DNAs (eccDNAs) are somatically mosaic and contribute to intercellular heterogeneity in normal and tumor cells. Because short eccDNAs are poorly chromatinized, we hypothesized that they are sequenced by tagmentation in ATAC-seq experiments without any enrichment of circular DNA. Indeed, ATAC-seq identified thousands of eccDNAs in cell lines that were validated by inverse PCR and by metaphase FISH. ATAC-seq in gliomas and glioblastomas identify hundreds of eccDNAs, including one containing the well-known EGFR gene amplicon from chr7. More than 18,000 eccDNAs, many carrying known cancer driver genes, are identified in a pan-cancer analysis of ATAC-seq libraries from 23 tumor types. Somatically mosaic eccDNAs are identified by ATAC-seq even before amplification is recognized by genome-wide copy number variation measurements. Thus, ATAC-seq is a sensitive method to detect eccDNA present in a tumor at the pre-amplification stage and can be used to predict resistance to therapy.
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48

Møller, Henrik D., Camilla E. Larsen, Lance Parsons, Anders Johannes Hansen, Birgitte Regenberg und Tobias Mourier. „Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons inSaccharomyces cerevisiae“. G3: Genes|Genomes|Genetics 6, Nr. 2 (17.12.2015): 453–62. http://dx.doi.org/10.1534/g3.115.025858.

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49

Wu, Xiaoqiong, Pu Li, Maimaitiaili Yimiti, Zhiqiu Ye, Xuqian Fang, Peizhan Chen und Zhidong Gu. „Identification and Characterization of Extrachromosomal Circular DNA in Plasma of Lung Adenocarcinoma Patients“. International Journal of General Medicine Volume 15 (Mai 2022): 4781–91. http://dx.doi.org/10.2147/ijgm.s363425.

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50

Alsford, N. S., M. Navarro, H. R. Jamnadass, H. Dunbar, M. Ackroyd, N. B. Murphy, K. Gull und K. Ersfeld. „The identification of circular extrachromosomal DNA in the nuclear genome of Trypanosoma brucei“. Molecular Microbiology 47, Nr. 2 (10.01.2003): 277–89. http://dx.doi.org/10.1046/j.1365-2958.2003.03266.x.

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