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Extrachromosomal DNA

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https://www.readbyqxmd.com/read/28803918/modeling-of-trex1-dependent-autoimmune-disease-using-human-stem-cells-highlights-l1-accumulation-as-a-source-of-neuroinflammation
#1
Charles A Thomas, Leon Tejwani, Cleber A Trujillo, Priscilla D Negraes, Roberto H Herai, Pinar Mesci, Angela Macia, Yanick J Crow, Alysson R Muotri
Three-prime repair exonuclease 1 (TREX1) is an anti-viral enzyme that cleaves nucleic acids in the cytosol, preventing accumulation and a subsequent type I interferon-associated inflammatory response. Autoimmune diseases, including Aicardi-Goutières syndrome (AGS) and systemic lupus erythematosus, can arise when TREX1 function is compromised. AGS is a neuroinflammatory disorder with severe and persistent intellectual and physical problems. Here we generated a human AGS model that recapitulates disease-relevant phenotypes using pluripotent stem cells lacking TREX1...
August 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28801529/silencing-of-repetitive-dna-is-controlled-by-a-member-of-an-unusual-caenorhabditis-elegans-gene-family
#2
Eduardo Leyva-Díaz, Nikolaos Stefanakis, Inés Carrera, Lori Glenwinkel, Guoqiang Wang, Monica Driscoll, Oliver Hobert
Repetitive DNA sequences are subject to gene silencing in various animal species. Under specific circumstances repetitive DNA sequences can escape such silencing. For example, when exogenously added, extrachromosomal DNA sequences that are stably inherited in multicopy repetitive arrays in the nematode Caenorhabditis elegans are frequently silenced in the germline, whereas such silencing often does not occur in the soma. This indicates that somatic cells might utilize factors that prevent repetitive DNA silencing...
August 11, 2017: Genetics
https://www.readbyqxmd.com/read/28801508/intricate-and-cell-type-specific-populations-of-endogenous-circular-dna-eccdna-in-caenorhabditis-elegans-and-homo-sapiens
#3
Massa J Shoura, Idan Gabdank, Loren Hansen, Jason Merker, Jason Gotlib, Stephen D Levene, Andrew Z Fire
Investigations aimed at defining the 3-D configuration of eukaryotic chromosomes have consistently encountered an endogenous population of chromosome-derived circular genomic DNA, referred to as extrachromosomal circular DNA (eccDNA). While the production, distribution, and activities of eccDNAs remain understudied, eccDNA formation from specific regions of the linear genome has profound consequences on the regulatory and coding capabilities for these regions. Here, we define eccDNA distributions in C. elegans and in three human cell types, utilizing a set of DNA-topology dependent approaches for enrichment and characterization...
August 11, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28755323/detection-of-the-alternative-lengthening-of-telomeres-pathway-in-malignant-gliomas-for-improved-molecular-diagnosis
#4
Anne Fogli, Marie-Véronique Demattei, Laetitia Corset, Catherine Vaurs-Barrière, Emmanuel Chautard, Julian Biau, Jean-Louis Kémény, Catherine Godfraind, Bruno Pereira, Toufik Khalil, Nathalie Grandin, Philippe Arnaud, Michel Charbonneau, Pierre Verrelle
Human malignant gliomas exhibit acquisition of either one of two telomere maintenance mechanisms, resulting from either reactivation of telomerase expression or activation of an alternative lengthening of telomeres (ALT) mechanism. In the present study, we analyzed 63 human malignant gliomas for the presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles) and measured telomerase expression, telomeric DNA content (Telo/Alu method), and telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular markers routinely used in clinical practice...
July 28, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28713341/prevalence-host-range-and-comparative-genomic-analysis-of-temperate-ochrobactrum-phages
#5
Claudia Jäckel, Stefan Hertwig, Holger C Scholz, Karsten Nöckler, Jochen Reetz, Jens A Hammerl
Ochrobactrum and Brucella are closely related bacteria that populate different habitats and differ in their pathogenic properties. Only little is known about mobile genetic elements in these genera which might be important for survival and virulence. Previous studies on Brucella lysogeny indicated that active phages are rare in this genus. To gain insight into the presence and nature of prophages in Ochrobactrum, temperate phages were isolated from various species and characterized in detail. In silico analyses disclosed numerous prophages in published Ochrobactrum genomes...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28696226/kaposi-s-sarcoma-associated-herpesvirus-stably-clusters-its-genomes-across-generations-to-maintain-itself-extrachromosomally
#6
Ya-Fang Chiu, Arthur U Sugden, Kathryn Fox, Mitchell Hayes, Bill Sugden
Genetic elements that replicate extrachromosomally are rare in mammals; however, several human tumor viruses, including the papillomaviruses and the gammaherpesviruses, maintain their plasmid genomes by tethering them to cellular chromosomes. We have uncovered an unprecedented mechanism of viral replication: Kaposi's sarcoma-associated herpesvirus (KSHV) stably clusters its genomes across generations to maintain itself extrachromosomally. To identify and characterize this mechanism, we developed two complementary, independent approaches: live-cell imaging and a predictive computational model...
July 10, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28687080/inhibition-of-rna-polymerase-ii-allows-controlled-mobilisation-of-retrotransposons-for-plant-breeding
#7
Michael Thieme, Sophie Lanciano, Sandrine Balzergue, Nicolas Daccord, Marie Mirouze, Etienne Bucher
BACKGROUND: Retrotransposons play a central role in plant evolution and could be a powerful endogenous source of genetic and epigenetic variability for crop breeding. To ensure genome integrity several silencing mechanisms have evolved to repress retrotransposon mobility. Even though retrotransposons fully depend on transcriptional activity of the host RNA polymerase II (Pol II) for their mobility, it was so far unclear whether Pol II is directly involved in repressing their activity...
July 7, 2017: Genome Biology
https://www.readbyqxmd.com/read/28673987/diatom-centromeres-suggest-a-mechanism-for-nuclear-dna-acquisition
#8
Rachel E Diner, Chari M Noddings, Nathan C Lian, Anthony K Kang, Jeffrey B McQuaid, Jelena Jablanovic, Josh L Espinoza, Ngocquynh A Nguyen, Miguel A Anzelmatti, Jakob Jansson, Vincent A Bielinski, Bogumil J Karas, Christopher L Dupont, Andrew E Allen, Philip D Weyman
Centromeres are essential for cell division and growth in all eukaryotes, and knowledge of their sequence and structure guides the development of artificial chromosomes for functional cellular biology studies. Centromeric proteins are conserved among eukaryotes; however, centromeric DNA sequences are highly variable. We combined forward and reverse genetic approaches with chromatin immunoprecipitation to identify centromeres of the model diatom Phaeodactylum tricornutum We observed 25 unique centromere sequences typically occurring once per chromosome, a finding that helps to resolve nuclear genome organization and indicates monocentric regional centromeres...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28671531/genomic-and-physiological-characterization-of-a-laboratory-isolated-acinetobacter-schindleri-ace-strain-that-quickly-and-efficiently-catabolizes-acetate
#9
Juan-Carlos Sigala, Brisa Paola Suárez, Alvaro R Lara, Sylvie Le Borgne, Patricia Bustos, Rosa Isela Santamaría, Víctor González, Alfredo Martinez
An Acinetobacter strain, designated ACE, was isolated in the laboratory. Phylogenetic tests and average nucleotide identity value comparisons suggested that ACE belongs to the species Acinetobacterschindleri. We report for the first time the complete genome sequence of an A. schindleri strain, which consists of a single circular chromosome of 3 001 209 bp with an overall DNA G+C content of 42.9 mol% and six plasmids that account for 266 844 bp of extrachromosomal material. The presence or absence of genes related to carbon catabolism and antibiotic resistance were in agreement with the phenotypic characterization of ACE...
July 3, 2017: Microbiology
https://www.readbyqxmd.com/read/28615293/looping-out-mechanism-for-resolution-of-replicative-stress-at-telomeres
#10
Tianpeng Zhang, Zepeng Zhang, Feng Li, Qian Hu, Haiying Liu, Mengfan Tang, Wenbin Ma, Junjiu Huang, Zhou Songyang, Yikang Rong, Shichuan Zhang, Benjamin Pc Chen, Yong Zhao
Repetitive DNA is prone to replication fork stalling, which can lead to genome instability. Here, we find that replication fork stalling at telomeres leads to the formation of t-circle-tails, a new extrachromosomal structure that consists of circular telomeric DNA with a single-stranded tail. Structurally, the t-circle-tail resembles cyclized leading or lagging replication intermediates that are excised from the genome by topoisomerase II-mediated cleavage. We also show that the DNA damage repair machinery NHEJ is required for the formation of t-circle-tails and for the resolution of stalled replication forks, suggesting that NHEJ, which is normally constitutively suppressed at telomeres, is activated in the context of replication stress...
August 2017: EMBO Reports
https://www.readbyqxmd.com/read/28608964/hbx-elevated-msl2-modulates-hbv-cccdna-through-inducing-degradation-of-apobec3b-to-enhance-hepatocarcinogenesis
#11
Yuen Gao, Jinyan Feng, Guang Yang, Shuqin Zhang, Yunxia Liu, Yanan Bu, Mingming Sun, Man Zhao, Fuquan Chen, Weiying Zhang, Lihong Ye, Xiaodong Zhang
Chronic hepatitis B virus (HBV) infection is a leading cause in the occurrence of hepatitis B, liver cirrhosis and liver cancer, in which nuclear HBV covalently closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence, plays crucial roles. In the present study, we explored the hypothesis that HBV X protein (HBx)-elevated male-specific lethal 2 (MSL2) activated HBV replication via modulating cccDNA in hepatoma cells, leading to hepatocarcinogenesis. Immunohistochemical analysis revealed that the expression of MSL2 was positively associated with that of HBV and was increased in the liver tissues of HBV-transgenic mice and clinical HCC patients...
June 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28569776/hiv-integrase-inhibitor-elvitegravir-impairs-rag-functions-and-inhibits-v-d-j-recombination
#12
Mayilaadumveettil Nishana, Namrata M Nilavar, Rupa Kumari, Monica Pandey, Sathees C Raghavan
Integrase inhibitors are a class of antiretroviral drugs used for the treatment of AIDS that target HIV integrase, an enzyme responsible for integration of viral cDNA into host genome. RAG1, a critical enzyme involved in V(D)J recombination exhibits structural similarity to HIV integrase. We find that two integrase inhibitors, Raltegravir and Elvitegravir, interfered with the physiological functions of RAGs such as binding, cleavage and hairpin formation at the recombination signal sequence (RSS), though the effect of Raltegravir was limited...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28550083/normal-and-cancerous-tissues-release-extrachromosomal-circular-dna-eccdna-into-the-circulation
#13
Pankaj Kumar, Laura W Dillon, Yoshiyuki Shibata, Amir A Jazaeri, David R Jones, Anindya Dutta
Cell-free circulating linear DNA is being explored for noninvasive diagnosis and management of tumors and fetuses, the so-called liquid biopsy. Previously, we observed the presence of small extrachromosomal circular DNA (eccDNA), called microDNA, in the nuclei of mammalian tissues and cell lines. Now, we demonstrate that cell-free microDNA derived from uniquely mapping regions of the genome is detectable in plasma and serum from both mice and humans and that they are significantly longer (30%-60% >250 bases) than cell-free circulating linear DNA (∼150 bases)...
May 26, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28549174/phosphorylated-sirt1-associates-with-replication-origins-to-prevent-excess-replication-initiation-and-preserve-genomic-stability
#14
Koichi Utani, Haiqing Fu, Sang-Min Jang, Anna B Marks, Owen K Smith, Ya Zhang, Christophe E Redon, Noriaki Shimizu, Mirit I Aladjem
Chromatin structure affects DNA replication patterns, but the role of specific chromatin modifiers in regulating the replication process is yet unclear. We report that phosphorylation of the human SIRT1 deacetylase on Threonine 530 (T530-pSIRT1) modulates DNA synthesis. T530-pSIRT1 associates with replication origins and inhibits replication from a group of 'dormant' potential replication origins, which initiate replication only when cells are subject to replication stress. Although both active and dormant origins bind T530-pSIRT1, active origins are distinguished from dormant origins by their unique association with an open chromatin mark, histone H3 methylated on lysine 4...
May 26, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28429320/euglena-gracilis-genome-and-transcriptome-organelles-nuclear-genome-assembly-strategies-and-initial-features
#15
ThankGod Echezona Ebenezer, Mark Carrington, Michael Lebert, Steven Kelly, Mark C Field
Euglena gracilis is a major component of the aquatic ecosystem and together with closely related species, is ubiquitous worldwide. Euglenoids are an important group of protists, possessing a secondarily acquired plastid and are relatives to the Kinetoplastidae, which themselves have global impact as disease agents. To understand the biology of E. gracilis, as well as to provide further insight into the evolution and origins of the Kinetoplastidae, we embarked on sequencing the nuclear genome; the plastid and mitochondrial genomes are already in the public domain...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28411218/the-conjugative-relaxase-trwc-promotes-integration-of-foreign-dna-in-the-human-genome
#16
Coral González-Prieto, Richard Gabriel, Christoph Dehio, Manfred Schmidt, Matxalen Llosa
Bacterial conjugation is a mechanism of horizontal DNA transfer. The relaxase TrwC of the conjugative plasmid R388 cleaves one strand of the transferred DNA at the oriT gene, covalently attaches to it, and leads the single-stranded DNA (ssDNA) into the recipient cell. In addition, TrwC catalyzes site-specific integration of the transferred DNA into its target sequence present in the genome of the recipient bacterium. Here, we report the analysis of the efficiency and specificity of the integrase activity of TrwC in human cells, using the type IV secretion system of the human pathogen Bartonella henselae to introduce relaxase-DNA complexes...
June 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28406973/tre5-a-retrotransposition-profiling-reveals-putative-rna-polymerase-iii-transcription-complex-binding-sites-on-the-dictyostelium-extrachromosomal-rdna-element
#17
Thomas Spaller, Marco Groth, Gernot Glöckner, Thomas Winckler
The amoeba Dictyostelium discoideum has a haploid genome in which two thirds of the DNA encodes proteins. Consequently, the space available for selfish mobile elements to expand without excess damage to the host genome is limited. The non-long terminal repeat retrotransposon TRE5-A maintains an active population in the D. discoideum genome and apparently adapted to this gene-dense environment by targeting positions ~47 bp upstream of tRNA genes that are devoid of protein-coding regions. Because only ~24% of tRNA genes are associated with a TRE5-A element in the reference genome, we evaluated whether TRE5-A retrotransposition is limited to this subset of tRNA genes...
2017: PloS One
https://www.readbyqxmd.com/read/28403180/amplification-of-a-transgene-within-a-long-array-of-replication-origins-favors-higher-gene-expression-in-animal-cells
#18
Kiwamu Ohsaki, Yusuke Ohgaki, Noriaki Shimizu
Plasmids with both a mammalian replication initiation region (IR) and a matrix attachment region (MAR) are spontaneously amplified in transfected cells, and generate extrachromosomal double minute (DM) or chromosomal homogeneously staining region (HSR). We previously isolated the shortest core IR (G5) required for gene amplification. In this study, we ligated the G5 DNA to create direct or inverted repeats, mixed the repeats with an expression plasmid, and transfected the mixture into human COLO 320DM or hamster CHO DG44 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28402891/brownian-ratchet-mechanism-for-faithful-segregation-of-low-copy-number-plasmids
#19
Longhua Hu, Anthony G Vecchiarelli, Kiyoshi Mizuuchi, Keir C Neuman, Jian Liu
Bacterial plasmids are extrachromosomal DNA that provides selective advantages for bacterial survival. Plasmid partitioning can be remarkably robust. For high-copy-number plasmids, diffusion ensures that both daughter cells inherit plasmids after cell division. In contrast, most low-copy-number plasmids need to be actively partitioned by a conserved tripartite ParA-type system. ParA is an ATPase that binds to chromosomal DNA; ParB is the stimulator of the ParA ATPase and specifically binds to the plasmid at a centromere-like site, parS...
April 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28366536/the-human-ctc1-stn1-ten1-complex-regulates-telomere-maintenance-in-alt-cancer-cells
#20
Chenhui Huang, Pingping Jia, Megan Chastain, Olga Shiva, Weihang Chai
Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle...
June 15, 2017: Experimental Cell Research
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