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Extrachromosomal DNA

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https://www.readbyqxmd.com/read/29329720/discoveries-of-extrachromosomal-circles-of-dna-in-normal-and-tumor-cells
#1
REVIEW
Teressa Paulsen, Pankaj Kumar, M Murat Koseoglu, Anindya Dutta
While the vast majority of cellular DNA in eukaryotes is contained in long linear strands in chromosomes, we have long recognized some exceptions like mitochondrial DNA, plasmids in yeasts, and double minutes (DMs) in cancer cells where the DNA is present in extrachromosomal circles. In addition, specialized extrachromosomal circles of DNA (eccDNA) have been noted to arise from repetitive genomic sequences like telomeric DNA or rDNA. Recently eccDNA arising from unique (nonrepetitive) DNA have been discovered in normal and malignant cells, raising interesting questions about their biogenesis, function and clinical utility...
January 9, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29260307/emerging-roles-for-sphingolipids-in-cellular-aging
#2
REVIEW
Pushpendra Singh, Rong Li
Aging is a gradual loss of physiological functions as organisms' progress in age. Although aging in multicellular organisms is complex, some fundamental mechanisms and pathways may be shared from the single cellular yeast to human. Budding yeast Saccharomyces cerevisiae has been established model system for aging studies. A yeast cell divides asymmetrically to produce two cells that differ in size and age. The one that is smaller coming from bud is a newborn cell that with a full replicative potential head irrespective of the replicative age of its mother-the larger cell from which the bud grows out before division...
December 19, 2017: Current Genetics
https://www.readbyqxmd.com/read/29246583/dna-structural-basis-for-fragility-at-peak-iii-of-bcl2-major-breakpoint-region-associated-with-t-14-18-translocation
#3
Saniya Javadekar, Rakhee Yadav, Sathees C Raghavan
Maintaining genome integrity is crucial for normal cellular functions. DNA double-strand breaks (DSBs), when unrepaired, can potentiate chromosomal translocations. t(14;18) translocation involving BCL2 gene on chromosome 18 and IgH loci at chromosome 14, could lead to follicular lymphoma. Molecular basis for fragility of translocation breakpoint regions is an active area of investigation. Previously, formation of non-B DNA structures like G-quadruplex, triplex, B/A transition were investigated at peak I of BCL2 major breakpoint region (MBR); however, it is less understood at peak III...
December 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29220507/assessing-the-heterogeneity-of-in-silico-plasmid-predictions-based-on-whole-genome-sequenced-clinical-isolates
#4
Cedric C Laczny, Valentina Galata, Achim Plum, Andreas E Posch, Andreas Keller
High-throughput next-generation shotgun sequencing of pathogenic bacteria is growing in clinical relevance, especially for chromosomal DNA-based taxonomic identification and for antibiotic resistance prediction. Genetic exchange is facilitated for extrachromosomal DNA, e.g. plasmid-borne antibiotic resistance genes. Consequently, accurate identification of plasmids from whole-genome sequencing (WGS) data remains one of the major challenges for sequencing-based precision medicine in infectious diseases. Here, we assess the heterogeneity of four state-of-the-art tools (cBar, PlasmidFinder, plasmidSPAdes and Recycler) for the in silico prediction of plasmid-derived sequences from WGS data...
December 5, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29162712/persistence-of-an-oncogenic-papillomavirus-genome-requires-cis-elements-from-the-viral-transcriptional-enhancer
#5
Koenraad Van Doorslaer, Dan Chen, Sandra Chapman, Jameela Khan, Alison A McBride
Human papillomavirus (HPV) genomes are replicated and maintained as extrachromosomal plasmids during persistent infection. The viral E2 proteins are thought to promote stable maintenance replication by tethering the viral DNA to host chromatin. However, this has been very difficult to prove genetically, as the E2 protein is involved in transcriptional regulation and initiation of replication, as well as its assumed role in genome maintenance. This makes mutational analysis of viral trans factors and cis elements in the background of the viral genome problematic and difficult to interpret...
November 21, 2017: MBio
https://www.readbyqxmd.com/read/29106411/extrachromosomal-telomere-repeat-dna-is-linked-to-alt-development-via-cgas-sting-dna-sensing-pathway
#6
Yi-An Chen, Yi-Ling Shen, Hsuan-Yu Hsia, Yee-Peng Tiang, Tzu-Ling Sung, Liuh-Yow Chen
Extrachromosomal telomere repeat (ECTR) DNA is unique to cancer cells that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, but the role of ECTRs in ALT development remains elusive. We found that induction of ECTRs in normal human fibroblasts activated the cGAS-STING-TBK1-IRF3 signaling axis to trigger IFNβ production and a type I interferon response, resulting in cell-proliferation defects. In contrast, ALT cancer cells are commonly defective in sensing cytosolic DNA. We found that STING expression was inhibited in ALT cancer cell lines and transformed ALT cells...
November 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29040510/genomic-fragmentation-and-extrachromosomal-telomeric-repeats-impact-assessment-of-telomere-length-in-human-spermatozoa-quantitative-experiments-and-systematic-review
#7
P Kurjanowicz, S Moskovtsev, C Librach
STUDY QUESTION: Can differences in DNA isolation alter assessment of sperm telomere length (spTL) and do they account for conflicting results in the literature on spTL and male fertility? SUMMARY ANSWER: DNA isolation methods preferentially include or exclude short, extrachromosomal (EC) telomere-specific sequences that alter spTL measurements, and are responsible for a proportion of the disparity observed between investigations. WHAT IS KNOWN ALREADY: The relationship between spTL and male fertility has become an active area of research...
November 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28887493/molecular-characterization-of-cell-free-eccdnas-in-human-plasma
#8
Jing Zhu, Fan Zhang, Meijun Du, Peng Zhang, Songbin Fu, Liang Wang
Extrachromosomal circular DNAs (eccDNAs) have been reported in most eukaryotes. However, little is known about the cell-free eccDNA profiles in circulating system such as blood. To characterize plasma cell-free eccDNAs, we performed sequencing analysis in 26 libraries from three blood donors and negative controls. We identified thousands of unique plasma eccDNAs in the three subjects. We observed proportional eccDNA increase with initial DNA input. The detected eccDNAs were also associated with circular DNA enrichment efficiency...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877255/characterization-of-the-microdna-through-the-response-to-chemotherapeutics-in-lymphoblastoid-cell-lines
#9
Pamela Mehanna, Vincent Gagné, Mathieu Lajoie, Jean-François Spinella, Pascal St-Onge, Daniel Sinnett, Ivan Brukner, Maja Krajinovic
Recently, a new class of extrachromosomal circular DNA, called microDNA, was identified. They are on average 100 to 400 bp long and are derived from unique non-repetitive genomic regions with high gene density. MicroDNAs are thought to arise from DNA breaks associated with RNA metabolism or replication slippage. Given the paucity of information on this entirely novel phenomenon, we aimed to get an additional insight into microDNA features by performing the microDNA analysis in 20 independent human lymphoblastoid cell lines (LCLs) prior and after treatment with chemotherapeutic drugs...
2017: PloS One
https://www.readbyqxmd.com/read/28870457/a-fluorogenic-c-neoformans-reporter-strain-with-a-robust-expression-of-m-cherry-expressed-from-a-safe-haven-site-in-the-genome
#10
Rajendra Upadhya, Woei C Lam, Brian T Maybruck, Maureen J Donlin, Andrew L Chang, Sarah Kayode, Kate L Ormerod, James A Fraser, Tamara L Doering, Jennifer K Lodge
C. neoformans is an encapsulated fungal pathogen with defined asexual and sexual life cycles. Due to the availability of genetic and molecular tools for its manipulation, it has become a model organism for studies of fungal pathogens, even though it lacks a reliable system for maintaining DNA fragments as extrachromosomal plasmids. To compensate for this deficiency, we identified a genomic gene-free intergenic region where heterologous DNA could be inserted by homologous recombination without adverse effects on the phenotype of the recipient strain...
November 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28803918/modeling-of-trex1-dependent-autoimmune-disease-using-human-stem-cells-highlights-l1-accumulation-as-a-source-of-neuroinflammation
#11
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...
September 7, 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
#12
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, 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...
October 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
#13
Massa J Shoura, Idan Gabdank, Loren Hansen, Jason Merker, Jason Gotlib, Stephen D Levene, Andrew Z Fire
Investigations aimed at defining the 3D 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 Caenorhabditis elegans and in three human cell types, utilizing a set of DNA topology-dependent approaches for enrichment and characterization...
October 5, 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
#14
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...
November 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28713341/prevalence-host-range-and-comparative-genomic-analysis-of-temperate-ochrobactrum-phages
#15
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
#16
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...
September 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28687080/inhibition-of-rna-polymerase-ii-allows-controlled-mobilisation-of-retrotransposons-for-plant-breeding
#17
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
#18
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
#19
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
#20
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
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