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https://www.readbyqxmd.com/read/28319081/guide-independent-dna-cleavage-by-archaeal-argonaute-from-methanocaldococcus-jannaschii
#1
Adrian Zander, Sarah Willkomm, Sapir Ofer, Marleen van Wolferen, Luisa Egert, Sabine Buchmeier, Sarah Stöckl, Philip Tinnefeld, Sabine Schneider, Andreas Klingl, Sonja-Verena Albers, Finn Werner, Dina Grohmann
Prokaryotic Argonaute proteins acquire guide strands derived from invading or mobile genetic elements, via an unknown pathway, to direct guide-dependent cleavage of foreign DNA. Here, we report that Argonaute from the archaeal organism Methanocaldococcus jannaschii (MjAgo) possesses two modes of action: the canonical guide-dependent endonuclease activity and a non-guided DNA endonuclease activity. The latter allows MjAgo to process long double-stranded DNAs, including circular plasmid DNAs and genomic DNAs...
March 20, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28314829/phosphorylation-of-wrinkled1-by-kin10-results-in-its-proteasomal-degradation-providing-a-link-between-energy-homeostasis-and-lipid-biosynthesis
#2
Zhiyang Zhai, Hui Liu, John Shanklin
WRINKLED1 (WRI1), a member of the APETALA2 (AP2) class of transcription factors, positively regulates glycolysis and lipid biosynthesis in Arabidopsis thaliana. Here we identify mechanistic links between KIN10, the major SUCROSE NON-FERMENTATION-1 (SNF1)-RELATED KINASE 1 (SnRK1) involved in sugar/energy homeostasis and the posttranslational regulation of WRI1. Transient expression of WRI1 with OLEOSIN1 (OLE1) in Nicotiana benthamiana stimulates triacylglycerol (TAG) accumulation, but their coexpression with KIN10 abrogates this effect by inducing proteasomal degradation of WRI1...
March 17, 2017: Plant Cell
https://www.readbyqxmd.com/read/28314590/inflammasome-activation-triggers-caspase-1-mediated-cleavage-of-cgas-to-regulate-responses-to-dna-virus-infection
#3
Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc(-/-) and Casp1(-/-) macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge...
March 8, 2017: Immunity
https://www.readbyqxmd.com/read/28284043/the-histone-variant-h3-3-claims-its-place-in-the-crowded-scene-of-epigenetics
#4
Daniele Bano, Antonia Piazzesi, Paolo Salomoni, Pierluigi Nicotera
Histones are evolutionarily conserved DNA-binding proteins. As scaffolding molecules, they significantly regulate the DNA packaging into the nucleus of all eukaryotic cells. As docking units, they influence the recruitment of the transcriptional machinery, thus establishing unique gene expression patterns that ultimately promote different biological outcomes. While canonical histones H3.1 and H3.2 are synthetized and loaded during DNA replication, the histone variant H3.3 is expressed and deposited into the chromatin throughout the cell cycle...
March 10, 2017: Aging
https://www.readbyqxmd.com/read/28277986/bardoxolone-methyl-inhibits-migration-and-metabolism-in-mcf7-cells
#5
Alaa Refaat, Chathyan Pararasa, Muhammed Arif, James E P Brown, Amtul Carmichael, Sameh S Ali, Hiroaki Sakurai, Helen R Griffiths
Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR...
February 2017: Free Radical Research
https://www.readbyqxmd.com/read/28260718/loss-of-setd2-but-not-h3k36me3-correlates-with-aggressive-clinicopathological-features-of-clear-cell-renal-cell-carcinoma-patients
#6
Lei Liu, Renbo Guo, Xiang Zhang, Yiran Liang, Feng Kong, Jue Wang, Zhonghua Xu
Recent studies facilitated by DNA sequencing identified the histone modifying gene SETD2 as the second most frequent mutant gene in sporadic clear cell renal cell carcinoma (ccRCC) patients. SETD2 functions as a tumor suppressor in ccRCC. However, its clinical association and biological functions are not fully delineated. The aim of this study is to evaluate the clinical significance of SETD2 in ccRCC patients. SETD2 and its canonical histone modification product H3K36me3 were analyzed by immunohistochemistry (IHC) in 155 ccRCC patients from two independent cohorts retrospectively...
March 6, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28260489/mechanisms-of-non-canonical-activation-of-ataxia-telangiectasia-mutated
#7
REVIEW
S V Khoronenkova
ATM is a master regulator of the cellular response to DNA damage. The classical mechanism of ATM activation involves its monomerization in response to DNA double-strand breaks, resulting in ATM-dependent phosphorylation of more than a thousand substrates required for cell cycle progression, DNA repair, and apoptosis. Here, new experimental evidence for non-canonical mechanisms of ATM activation in response to stimuli distinct from DNA double-strand breaks is discussed. It includes cytoskeletal changes, chromatin modifications, RNA-DNA hybrids, and DNA single-strand breaks...
December 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28260487/structure-properties-and-biological-relevance-of-the-dna-and-rna-g-quadruplexes-overview-50-years-after-their-discovery
#8
N G Dolinnaya, A M Ogloblina, M G Yakubovskaya
G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding-unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA-RNA G4s are discussed...
December 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28251877/genomic-landscape-of-cpg-rich-elements-in-human
#9
Vladimir N Babenko, Irina V Chadaeva, Yuriy L Orlov
BACKGROUND: The studies on CpG islands (CGI) and Alu elements functions, evolution, and distribution in the genome started since the discovery in nineteen eighties (1981, 1986, correspondingly). Their highly skewed genome wide distribution implies the non-random retrotransposition pattern. Besides CGIs in gene promoters, CGIs clusters were observed in the homeobox gene regions and in the macrosatellites, but the whole picture of their distribution specifics was not grasped. Attempts to identify any causative features upon their (genome wide) distribution, such as the DNA context mediated preferred insertion sites of Alu repeats, have been made to ascribe their clusters location...
February 7, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28251405/differential-decrease-in-soluble-and-dna-bound-telomerase-in-senescent-human-fibroblasts
#10
Snir Yehuda, Hagai Yanai, Esther Priel, Vadim E Fraifeld
The role of telomere shortening in the induction of replicative cellular senescence (CS) is well known and as a result, the involvement of telomerase and in particular its catalytic subunit, the telomerase reverse transcriptase (TERT) in CS has also been investigated. However, the majority of studies were conducted on cells that generally express high levels of TERT (cancer and immortalized cells) while the role of telomerase in CS in normal cells has been investigated to a much lesser extent. In particular, it was reported that active TERT is expressed in early passages of cultured human keratinocytes but rapidly diminished towards entry to CS, without telomere shortening...
March 1, 2017: Biogerontology
https://www.readbyqxmd.com/read/28244221/genomic-rearrangements-induced-by-unscheduled-dna-double-strand-breaks-in-somatic-mammalian-cells
#11
REVIEW
Ayeong So, Tangui Le Guen, Bernard S Lopez, Josée Guirouilh-Barbat
DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to profound genome rearrangements and/or cell death. DSBs routinely occur in genomes due to endogenous or exogenous stresses. Efficient repair systems, canonical non-homologous end-joining and homologous recombination, exist in the cell and not only ensure the maintenance of genome integrity but also, via specific programmed DNA double-strand breaks, permit its diversity and plasticity. However, these repair systems need to be tightly controlled because they can also generate genomic rearrangements...
February 28, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28223045/crystal-structures-reveal-a-new-and-novel-foxo1-binding-site-within-the-human-glucose-6-phosphatase-catalytic-subunit-1-gene-promoter
#12
Puja Singh, Eun Hee Han, James A Endrizzi, Richard M O'Brien, Young-In Chi
Human glucose-6-phosphatase plays a vital role in blood glucose homeostasis and holds promise as a therapeutic target for diabetes. Expression of its catalytic subunit gene 1 (G6PC1) is tightly regulated by metabolic-response transcription factors such as FoxO1 and CREB. Although at least three potential FoxO1 binding sites (insulin response elements, IREs) and one CREB binding site (cAMP response element, CRE) within the proximal region of the G6PC1 promoter have been identified, the interplay between FoxO1 and CREB and between FoxO1 bound at multiple IREs has not been well characterized...
February 20, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28219718/a-novel-regulatory-role-of-rgs4-in-stat5b-activation-neurite-outgrowth-and-neuronal-differentiation
#13
Paschalina Pallaki, Eirini-Maria Georganta, Ioannis Serafimidis, Maria-Pagona Papakonstantinou, Vassilis Papanikolaou, Sofia Koutloglou, Elsa Papadimitriou, Adamantia Agalou, Aggeliki Tserga, Alexandra Simeonof, Dimitra Thomaidou, Maria Gaitanou, Zafiroula Georgoussi
The Regulator of G protein Signalling 4 (RGS4) is a multitask protein that interacts with and negatively modulates opioid receptor signalling. Previously, we showed that the δ-opioid receptor (δ-OR) forms a multiprotein signalling complex consisting of Gi/Go proteins and the Signal Transducer and Activator of Transcription 5B (STAT5B) that leads to neuronal differentiation and neurite outgrowth upon δ-ΟR activation. Here, we investigated whether RGS4 could participate in signalling pathways to regulate neurotropic events...
February 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28187685/geometric-patterns-for-neighboring-bases-near-the-stacked-state-in-nucleic-acid-strands
#14
Ada Sedova, Nilesh K Banavali
Structural variation in base stacking has been analyzed frequently in isolated double helical contexts for nucleic acids, but not as often in nonhelical geometries or in complex biomolecular environments. In this study, conformations of two neighboring bases near their stacked state in any environment are comprehensively characterized for single-strand dinucleotide (SSD) nucleic acid crystal structure conformations. An ensemble clustering method is used to identify a reduced set of representative stacking geometries based on pairwise distances between select atoms in consecutive bases, with multiple separable conformational clusters obtained for categories divided by nucleic acid type (DNA/RNA), SSD sequence, stacking face orientation, and the presence or absence of a protein environment...
March 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28169375/the-rb1-tumour-suppressor-gene-modifies-telomeric-chromatin-architecture-by-regulating-terra-expression
#15
I Gonzalez-Vasconcellos, R Schneider, N Anastasov, S Alonso-Rodriguez, B Sanli-Bonazzi, J L Fernández, M J Atkinson
The tumour suppressor gene (Rb1) is necessary for the maintenance of telomere integrity in osteoblastic cells. We now show that the compaction of telomeric chromatin and the appropriate histone modifications of telomeric DNA are both dependent upon Rb1-mediated transcription of the telomere-derived long non-coding RNA TERRA. Expression of TERRA was reduced in Rb1 haploinsufficient cells, and further decreased by shRNA-mediated reduction of residual Rb1 expression. Restoration of Rb1 levels through lentiviral transduction was sufficient to reestablish both transcription of TERRA and condensation of telomeric chromatin...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28166722/integration-of-vdr-genome-wide-binding-and-gwas-genetic-variation-data-reveals-co-occurrence-of-vdr-and-nf-%C3%AE%C2%BAb-binding-that-is-linked-to-immune-phenotypes
#16
Prashant K Singh, Patrick R van den Berg, Mark D Long, Angie Vreugdenhil, Laurie Grieshober, Heather M Ochs-Balcom, Jianmin Wang, Sylvie Delcambre, Sami Heikkinen, Carsten Carlberg, Moray J Campbell, Lara E Sucheston-Campbell
BACKGROUND: The nuclear hormone receptor superfamily acts as a genomic sensor of diverse signals. Their actions are often intertwined with other transcription factors. Nuclear hormone receptors are targets for many therapeutic drugs, and include the vitamin D receptor (VDR). VDR signaling is pleotropic, being implicated in calcaemic function, antibacterial actions, growth control, immunomodulation and anti-cancer actions. Specifically, we hypothesized that the biologically significant relationships between the VDR transcriptome and phenotype-associated biology could be discovered by integrating the known VDR transcription factor binding sites and all published trait- and disease-associated SNPs...
February 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28164088/effective-implementation-of-novel-met-pharmacodynamic-assays-in-translational-studies
#17
REVIEW
Apurva K Srivastava, Tony Navas, William G Herrick, Melinda G Hollingshead, Donald P Bottaro, James H Doroshow, Ralph E Parchment
MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies. The capability to interrogate oncogenic mutations in MET via circulating tumor DNA (ctDNA) provides an important advancement in identification and stratification of patients for MET therapy...
January 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28163277/cloning-localization-and-focus-formation-at-dna-damage-sites-of-canine-ku70
#18
Manabu Koike, Yasutomo Yutoku, Aki Koike
Understanding the molecular mechanisms of DNA double-strand break (DSB) repair machinery, specifically non-homologous DNA-end joining (NHEJ), is crucial for developing next-generation radiotherapies and common chemotherapeutics for human and animal cancers. The localization, protein-protein interactions and post-translational modifications of core NHEJ factors, might play vital roles for regulation of NHEJ activity. The human Ku heterodimer (Ku70/Ku80) is a core NHEJ factor in the NHEJ pathway and is involved in sensing of DSBs...
February 6, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28161934/identification-of-diverse-adenosine-to-inosine-rna-editing-subtypes-in-colorectal-cancer
#19
Si-Hyun Lee, Hwang-Phill Kim, Jun-Kyu Kang, Sang-Hyun Song, Sae-Won Han, Tae-You Kim
Purpose: RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-Inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer. Therefore, this study was conducted to identify diverse RNA editing in colorectal cancer. Materials and Methods: We compared transcriptome data of 39 colorectal cancer (CRC) samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions...
January 25, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28134821/non-canonical-replication-initiation-you-re-fired
#20
REVIEW
Bazilė Ravoitytė, Ralf Erik Wellinger
The division of prokaryotic and eukaryotic cells produces two cells that inherit a perfect copy of the genetic material originally derived from the mother cell. The initiation of canonical DNA replication must be coordinated to the cell cycle to ensure the accuracy of genome duplication. Controlled replication initiation depends on a complex interplay of cis-acting DNA sequences, the so-called origins of replication (ori), with trans-acting factors involved in the onset of DNA synthesis. The interplay of cis-acting elements and trans-acting factors ensures that cells initiate replication at sequence-specific sites only once, and in a timely order, to avoid chromosomal endoreplication...
January 27, 2017: Genes
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