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Extrachromosomal DNA

Xuan Qin, Chuan Zhou, Danielle M Zerr, Amanda Adler, Amin Addetia, Shuhua Yuan, Alexander L Greninger
Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis (CF) are known to differ from those associated with non-CF hosts by colony morphology, drug susceptibility patterns, and genomic hypermutability. Pseudomonas aeruginosa isolates from CF patients have long been recognized for their overall reduced rate of antimicrobial susceptibility, but their intraclonal MIC heterogeneity has long been overlooked. Using two distinct cohorts of clinical strains ( n = 224 from 56 CF patients, n = 130 from 68 non-CF patients) isolated in 2013, we demonstrated profound Etest MIC heterogeneity in CF P...
March 2018: MSphere
Laura Monteonofrio, Davide Valente, Manuela Ferrara, Serena Camerini, Roberta Miscione, Marco Crescenzi, Cinzia Rinaldo, Silvia Soddu
Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14...
March 22, 2018: Oncogene
Amanda C Carroll, Alex Wong
Plasmids are extrachromosomal DNA elements that can be found throughout bacteria, as well as in other domains of life. Nonetheless, the evolutionary processes underlying the persistence of plasmids are incompletely understood. Bacterial plasmids may encode genes for traits which are sometimes beneficial to their hosts, such as antimicrobial resistance, virulence, heavy metal tolerance, and the catabolism of unique nutrient sources. In the absence of selection for these traits, however, plasmids generally impose a fitness cost on their hosts...
March 21, 2018: Canadian Journal of Microbiology
Diane Penndorf, Otto W Witte, Alexandra Kretz
The pathophysiology of amyotrophic lateral sclerosis (ALS) is particularly challenging due to the heterogeneity of its clinical presentation and the diversity of cellular, molecular and genetic peculiarities involved. Molecular insights unveiled several novel genetic factors to be inherent in both familial and sporadic disease entities, whose characterizations in terms of phenotype prediction, pathophysiological impact and putative prognostic value are a topic of current researches. However, apart from genetically well-defined high-confidence and other susceptibility loci, the role of DNA damage and repair strategies of the genome as a whole, either elicited as a direct consequence of the underlying genetic mutation or seen as an autonomous parameter, in the initiation and progression of ALS, and the different cues involved in either process are still incompletely understood...
February 2018: Neural Regeneration Research
Suneeta Chimalapati, Marcela de Souza Santos, Kelly Servage, Nicole J De Nisco, Ankur B Dalia, Kim Orth
The Gram-negative bacterium Vibrio parahaemolyticus is an opportunistic human pathogen and the leading cause of seafood borne acute gastroenteritis worldwide. Recently, this bacterium was implicated as the etiologic agent of a severe shrimp disease with consequent devastating outcomes to shrimp farming. In both cases, acquisition of genetic material via horizontal transfer provided V. parahaemolyticus with new virulence tools to cause disease. Dissecting the molecular mechanisms of V. parahaemolyticus pathogenesis often requires manipulating its genome...
March 19, 2018: Journal of Bacteriology
Henrik Devitt Møller, Marghoob Mohiyuddin, Iñigo Prada-Luengo, M Reza Sailani, Jens Frey Halling, Peter Plomgaard, Lasse Maretty, Anders Johannes Hansen, Michael P Snyder, Henriette Pilegaard, Hugo Y K Lam, Birgitte Regenberg
The human genome is generally organized into stable chromosomes, and only tumor cells are known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccDNAs). However, it must be expected that kb eccDNAs exist in normal cells as a result of mutations. Here, we purify and sequence eccDNAs from muscle and blood samples from 16 healthy men, detecting ~100,000 unique eccDNA types from 16 million nuclei. Half of these structures carry genes or gene fragments and the majority are smaller than 25 kb...
March 14, 2018: Nature Communications
Dal-Hoe Koo, William T Molin, Christopher A Saski, Jiming Jiang, Karthik Putta, Mithila Jugulam, Bernd Friebe, Bikram S Gill
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...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ian J Groves, Nicholas Coleman
Human papillomavirus (HPV) infection is associated with ~5% of all human cancers, including a range of squamous cell carcinomas (SCCs). Persistent infection by high-risk HPVs (HRHPVs) is associated with the integration of virus genomes (which are usually stably maintained as extrachromosomal episomes) into host chromosomes. Although HRHPV integration rates differ across human sites of infection, this process appears to be an integral event in HPV-associated neoplastic progression, leading to deregulation of virus oncogene expression, host gene expression modulation and further genomic instability...
February 14, 2018: Journal of Pathology
Javier Martinez-Picado, Ryan Zurakowski, María José Buzón, Mario Stevenson
Reverse transcription of HIV-1 results in the generation of a linear cDNA that serves as the precursor to the integrated provirus. Other classes of extrachromosomal viral cDNA molecules can be found in acutely infected cells including the 1-LTR and 2-LTR circles of viral DNA, also referred as episomal HIV-1 DNA. Circulating CD4+ T-cells of treatment-naïve individuals contain significant levels of unintegrated forms of HIV-1 DNA. However, the importance of episomal HIV-1 DNA in the study of viral persistence during antiviral therapy (ART) is debatable...
January 30, 2018: Retrovirology
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
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
Saniya M 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...
March 2018: Biochimica et Biophysica Acta
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
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
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...
December 2017: Nature Structural & Molecular Biology
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
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
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
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
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
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