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https://www.readbyqxmd.com/read/29912891/-c2g4-n-repeat-expansion-sequences-from-the-c9orf72-gene-form-an-unusual-dna-higher-order-structure-in-the-ph-range-of-5-6
#1
Prince Kumar Lat, Dipankar Sen
Massive expansion of a DNA hexanucleotide sequence repeat (C2G4) within the human C9orf72 gene has been linked to a number of neurodegenerative diseases. In sodium or potassium salt solutions, single-stranded d(C2G4)n DNAs fold to form G-quadruplexes. We have found that in magnesium or lithium salt solutions, especially under slightly acidic conditions, d(C2G4)n oligonucleotides fold to form a distinctive higher order structure whose most striking feature is an "inverted" circular dichroism spectrum, which is distinguishable from the spectrum of the left handed DNA double-helix, Z-DNA...
2018: PloS One
https://www.readbyqxmd.com/read/29753769/fish-samhd1-performs-as-an-activator-for-ifn-expression
#2
Meifeng Li, Xiaowen Xu, Zeyin Jiang, Changxin Liu, Xiao Shi, Guoqin Qi, Yinping Li, Xin Chen, Qingli Huang, Huiling Mao, Chengyu Hu
As a host limiting factor, Sterile Alpha Motif and Histidine-Aspartate Domain 1 protein (SAMHD1) is associated with IRF3-mediated antiviral and apoptotic responses in mammals. However, the antiviral mechanism of SAMHD1 remains indistinct in fish. In this study, we found the expression of Ctenopharyngodon idella SAMHD1 (MF326081) was up-regulated after transfection with poly I:C (dsRNA analog), B-DNA or Z-DNA into C. idella kidney cells (CIKs), but these expression profiles had no obvious change when the cells were incubated with these nucleic acids...
May 10, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29721152/tumor-cell-death-after-electrotransfer-of-plasmid-dna-is-associated-with-cytosolic-dna-sensor-upregulation
#3
Katarina Znidar, Masa Bosnjak, Nina Semenova, Olga Pakhomova, Loree Heller, Maja Cemazar
Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA)...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29684182/visualizing-structure-mediated-interactions-in-supercoiled-dna-molecules
#4
Shane Scott, Zhi Ming Xu, Fedor Kouzine, Daniel J Berard, Cynthia Shaheen, Barbara Gravel, Laura Saunders, Alexander Hofkirchner, Catherine Leroux, Jill Laurin, David Levens, Craig J Benham, Sabrina R Leslie
We directly visualize the topology-mediated interactions between an unwinding site on a supercoiled DNA plasmid and a specific probe molecule designed to bind to this site, as a function of DNA supercoiling and temperature. The visualization relies on containing the DNA molecules within an enclosed array of glass nanopits using the Convex Lens-induced Confinement (CLiC) imaging method. This method traps molecules within the focal plane while excluding signal from out-of-focus probes. Simultaneously, the molecules can freely diffuse within the nanopits, allowing for accurate measurements of exchange rates, unlike other methods which could introduce an artifactual bias in measurements of binding kinetics...
May 18, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29617273/binding-interactions-of-zinc-cationic-porphyrin-with-duplex-dna-from-b-dna-to-z-dna
#5
Tingxiao Qin, Kunhui Liu, Di Song, Chunfan Yang, Hongmei Zhao, Hongmei Su
Recognition of unusual left-handed Z-DNA by specific binding of small molecules is crucial for understanding biological functions in which this particular structure participates. Recent investigations indicate that zinc cationic porphyrin (ZnTMPyP4) is promising as a probe for recognizing Z-DNA due to its characteristic chiroptical properties upon binding with Z-DNA. However, binding mechanisms of the ZnTMPyP4/Z-DNA complex remain unclear. By employing time-resolved UV-visible absorption spectroscopy in conjunction with induced circular dichroism (ICD), UV-vis, and fluorescence measurements, we examined the binding interactions of ZnTMPyP4 towards B-DNA and Z-DNA...
April 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29584891/unveiling-the-pathway-to-z-dna-in-the-protein-induced-b-z-transition
#6
Sook Ho Kim, So-Hee Lim, Ae-Ree Lee, Do Hoon Kwon, Hyun Kyu Song, Joon-Hwa Lee, Minhaeng Cho, Albert Johner, Nam-Kyung Lee, Seok-Cheol Hong
Left-handed Z-DNA is an extraordinary conformation of DNA, which can form by special sequences under specific biological, chemical or physical conditions. Human ADAR1, prototypic Z-DNA binding protein (ZBP), binds to Z-DNA with high affinity. Utilizing single-molecule FRET assays for Z-DNA forming sequences embedded in a long inactive DNA, we measure thermodynamic populations of ADAR1-bound DNA conformations in both GC and TG repeat sequences. Based on a statistical physics model, we determined quantitatively the affinities of ADAR1 to both Z-form and B-form of these sequences...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29532848/c8-guanine-modifications-effect-on-z-dna-formation-and-its-role-in-cancer
#7
REVIEW
V Vongsutilers, P M Gannett
Base modifications are known to affect the structure and function of DNA. C8-guanine adducts from various carcinogenic compounds have been shown to be potent Z-DNA inducers. Hence, it has been hypothesized that Z-DNA plays a role in cancer and other genetic diseases. In this comprehensive review, Z-DNA and the effect of prevalent C8-guanine adducts on the B-Z transition are addressed. The discoveries of Z-DNA binding proteins including ADAR1, E3L, DLM1, and PKZ have suggested the relevance of Z-DNA in living systems...
March 28, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29348591/relapsing-remitting-multiple-sclerosis-diagnosis-from-cerebrospinal-fluids-via-fourier-transform-infrared-spectroscopy-coupled-with-multivariate-analysis
#8
Dilek Yonar, Levent Ocek, Bedile Irem Tiftikcioglu, Yasar Zorlu, Feride Severcan
Multiple sclerosis (MS) is a chronic, progressive, inflammatory and degenerative disease of central nervous system. Here, we aimed to develop a method for differential diagnosis of Relapsing-Remitting MS (RRMS) and clinically isolated syndrome (CIS) patients, as well as to identify CIS patients who will progress to RRMS, from cerebrospinal fluid (CSF) by infrared (IR) spectroscopy and multivariate analysis. Spectral analyses demonstrated significant differences in the molecular contents, especially in the lipids and Z conformation of DNA of CSF from CIS, CIS to RRMS transformed (TCIS) and RRMS groups...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343810/mitochondrial-dna-damage-and-subsequent-activation-of-z-dna-binding-protein-1-links-oxidative-stress-to-inflammation-in-epithelial-cells
#9
Bartosz Szczesny, Michela Marcatti, Akbar Ahmad, Mauro Montalbano, Attila Brunyánszki, Sofia-Iris Bibli, Andreas Papapetropoulos, Csaba Szabo
This report identifies mitochondrial DNA (mtDNA) as a target and active mediator that links low-level oxidative stress to inflammatory response in pulmonary epithelial cells. Extrusion of mtDNA into the bronchoalveolar lavage fluid occurs as an early event in mice subjected to cigarette smoke injury, concomitantly with the depletion of mtDNA in the lung tissue. In cultured lung epithelial cells, prolonged, low-level oxidative stress damages the mtDNA, without any detectable damage to the nuclear DNA. In turn, cellular depletion of the mtDNA occurs, together with a transient remodeling of cellular bioenergetics and morphology - all without any detectable impairment in overall cell viability...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339104/region-specific-innate-antiviral-responses-of-the-human-epididymis
#10
James A Browne, Shih-Hsing Leir, Scott E Eggener, Ann Harris
Viral infections of the epididymis are associated with epididymitis, which damages the epithelium and impairs fertility. We showed previously that innate immune response genes were differentially expressed in the corpus and cauda region of the human epididymis in comparison to the caput. Here we investigate the antiviral defense response mechanisms of human epididymis epithelial (HEE) cells. Toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are enriched in HEE cells from the corpus and cauda region...
January 13, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29321274/irf1-is-a-transcriptional-regulator-of-zbp1-promoting-nlrp3-inflammasome-activation-and-cell-death-during-influenza-virus-infection
#11
Teneema Kuriakose, Min Zheng, Geoffrey Neale, Thirumala-Devi Kanneganti
Innate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms, including the nucleotide and oligomerization domain, leucine-rich repeat-containing protein family, pyrin domain containing 3 (NLRP3) inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. In this study, we demonstrate the role of IFN regulatory factor (IRF)1 in promoting NLRP3 inflammasome activation and cell death during IAV infection...
February 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29236673/zbp1-innate-sensor-regulating-cell-death-and-inflammation
#12
REVIEW
Teneema Kuriakose, Thirumala-Devi Kanneganti
Z-DNA-binding protein 1 (ZBP1), initially reported as an interferon (IFN)-inducible tumor-associated protein, harbors nucleic acid-binding domains for left-handed helix (Z-form) and receptor-interacting protein homotypic interaction motif (RHIM) domains for protein homotypic interactions. Recent studies have identified ZBP1 as an innate sensor of viral infections and a target of viral evasion strategies, regulating cell death, inflammasome activation, and proinflammatory responses. ZBP1 also functions during development and can trigger perinatal lethality when its RHIM-dependent interactions are not restricted...
February 2018: Trends in Immunology
https://www.readbyqxmd.com/read/29185909/the-effects-of-a-neutral-cosolute-on-the-b-to-z-transition-for-dna-duplexes-incorporating-both-cg-and-ca-steps
#13
Pakinee Phromsiri, Rebecca R Gerling, Joshua M Blose
In the cell, nearly 40% of the volume is occupied by macromolecular crowding agents and smaller osmolytes accumulate in response to environmental stresses. Of particular interest is the influence of osmolytes on the transition of the right-handed B-DNA to the left-handed Z-DNA. Due to the correlation between Z-DNA formation potential and regions of active transcription, Z-DNA is believed to serve a vital role in the transcription process, and changes in osmolyte concentration may influence transcription as a part of the stress response...
November 2, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/29102935/ft-ir-spectroscopy-study-in-early-diagnosis-of-skin-cancer
#14
Maria Kyriakidou, Jane Anastassopoulou, Aristeidis Tsakiris, Maria Koui, Theophile Theophanides
BACKGROUND/AIM: Mid-infrared spectroscopy (4000-500 cm-1 ) was used to analyze the spectral changes and differences of the characteristic absorption bands of the skin components due to cancer development for early clinical diagnosis. MATERIALS AND METHODS: Human biopsies from basal cell carcinoma, malignant melanoma, and nevus were used, while normal skin tissue served as a control. RESULTS: The high quality of Fourier-transform infrared (FT-IR) spectra showed that upon cancer development the intensity of the absorption band at approximately 3062 cm-1 was increased, indicating that most of the proteins had the configuration of amide B and the β-sheet protein structure predominated...
November 2017: In Vivo
https://www.readbyqxmd.com/read/29095165/four-highly-pseudosymmetric-and-or-twinned-structures-of-d-cgcgcg-2-extend-the-repertoire-of-crystal-structures-of-z-dna
#15
Zhipu Luo, Zbigniew Dauter, Miroslaw Gilski
DNA oligomer duplexes containing alternating cytosines and guanines in their sequences tend to form left-handed helices of the Z-DNA type, with the sugar and phosphate backbone in a zigzag conformation and a helical repeat of two successive nucleotides. Z-DNA duplexes usually crystallize as hexagonally arranged parallel helical tubes, with various relative orientations and translation of neighboring duplexes. Four novel high-resolution crystal structures of d(CGCGCG)2 duplexes are described here. They are characterized by a high degree of pseudosymmetry and/or twinning, with three or four independent duplexes differently oriented in a monoclinic P21 lattice of hexagonal metric...
November 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/29073079/inhibition-of-dai-dependent-necroptosis-by-the-z-dna-binding-domain-of-the-vaccinia-virus-innate-immune-evasion-protein-e3
#16
Heather Koehler, Samantha Cotsmire, Jeffrey Langland, Karen V Kibler, Daniel Kalman, Jason W Upton, Edward S Mocarski, Bertram L Jacobs
Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which contains an N-terminal Z-nucleic acid binding (Zα) domain that is critical for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the Zα domain of E3 (VACV-E3LΔ83N) induced rapid RIPK3-dependent cell death in IFN-treated L929 cells. Cell death was inhibited by the RIPK3 inhibitor, GSK872, and infection with this mutant virus led to phosphorylation and aggregation of MLKL, the executioner of necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29046345/endoplasmic-reticulum-transmembrane-proteins-zdhhc1-and-sting-both-act-as-direct-adaptors-for-irf3-activation-in-teleost
#17
Xiaowen Xu, Meifeng Li, Zhen Wu, Haizhou Wang, Liqiang Wang, Keyi Huang, Xiancheng Liu, Qunhao Hou, Gang Lin, Chengyu Hu
IFN regulatory factor (IRF)3 is a central regulator for IFN-β expression in different types of pathogenic infections. Mammals have various pathogenic sensors that are involved in monitoring pathogen intrusions. These sensors can trigger IRF3-mediated antiviral responses through different pathways. Endoplasmic reticulum-associated proteins stimulator of IFN gene (STING) and zinc finger DHHC-type containing 1 (ZDHHC1) are critical mediators of IRF3 activation in response to viral DNA infections. In this study, grass carp STING and ZDHHC1 were found to have some similar molecular features and subcellular localization, and both were upregulated upon stimulation with polyinosinic:polycytidylic acid, B-DNA, or Z-DNA...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29017946/cloning-and-expression-of-malabar-grouper-epinephelus-malabaricus-adar1-gene-in-response-to-immune-stimulants-and-nervous-necrosis-virus
#18
Thirunavukkarasu Periyasamy, Joan Tang Xiao Joe, Ming-Wei Lu
ADARs are RNA editing catalysts that bind double-stranded RNA and convert adenosine to inosine, a process that can lead to destabilization of dsRNA structures and suppression of mRNA translation. In mammals, ADAR1 genes are involved in various cellular pathways, including interferon (IFN)-mediated response. However, the function of fish ADAR1 remains unclear. We report here the cloning of ADAR1 in Malabar grouper (Epinephelus malabaricus) (MgADAR1) and its response to various immune stimulants. The MgADAR1 cDNA is 5371-bp long, consisting of an open reading frame encoding a putative protein of 1381 amino acids, a 235-nt 5'-terminal untranslated region (UTR), and a 990-nt 3'-UTR...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28960389/the-other-face-of-an-editor-adar1-functions-in-editing-independent-ways
#19
REVIEW
Konstantin Licht, Michael F Jantsch
The RNA editing enzyme ADAR1 seemingly has more functions besides RNA editing. Mouse models lacking ADAR1 and sensors of foreign RNA show that RNA editing by ADAR1 plays a crucial role in the innate immune response. Still, RNA editing alone cannot explain all observed phenotypes. Thus, additional roles for ADAR1 must exist. Binding of ADAR1 to RNA is independent of its RNA editing function. Thus, ADAR1 may compete with other RNA-binding proteins. A very recent manuscript elaborates on this and reports competition of ADAR1 with STAUFEN1, thereby modulating RNA-degradation...
September 28, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28924040/a-b-z-junction-induced-by-an-a-%C3%A2-a-mismatch-in-gac-repeats-in-the-gene-for-cartilage-oligomeric-matrix-protein-promotes-binding-with-the-hz%C3%AE-adar1-protein
#20
Narendar Kolimi, Yogeeshwar Ajjugal, Thenmalarchelvi Rathinavelan
GAC repeat expansion from five to seven in the exonic region of the gene for cartilage oligomeric matrix protein (COMP) leads to pseudoachondroplasia, a skeletal abnormality. However, the molecular mechanism by which GAC expansions in the COMP gene lead to skeletal dysplasias is poorly understood. Here we used molecular dynamics simulations, which indicate that an A … A mismatch in a d(GAC)6 ·d(GAC)6 duplex induces negative supercoiling, leading to a local B-to-Z DNA transition. This transition facilitates the binding of d(GAC)7 ·d(GAC)7 with the Zα-binding domain of human adenosine deaminase acting on RNA 1 (ADAR1, hZαADAR1 ), as confirmed by CD, NMR, and microscale thermophoresis studies...
November 17, 2017: Journal of Biological Chemistry
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