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DNA-binding proteins

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https://www.readbyqxmd.com/read/28822069/characterization-of-ofloxacin-interaction-with-mutated-a91v-quinolone-resistance-determining-region-of-dna-gyrase-in-mycobacterium-leprae-through-computational-simulation
#1
J Nisha, V Shanthi
Mycobacterium leprae, the causal agent of leprosy is non-cultivable in vitro. Thus, the assessment of antibiotic activity against Mycobacterium leprae depends primarily upon the time-consuming mouse footpad system. The GyrA protein of Mycobacterium leprae is the target of the antimycobacterial drug, Ofloxacin. In recent times, the GyrA mutation (A91V) has been found to be resistant to Ofloxacin. This phenomenon has necessitated the development of new, long-acting antimycobacterial compounds. The underlying mechanism of drug resistance is not completely known...
August 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28821613/the-rir-motif-in-the-scaffold-protein-xrcc1-mediates-a-low-affinity-interaction-with-polynucleotide-kinase-phosphatase-pnkp-during-dna-single-strand-break-repair
#2
Claire Breslin, Rajam S Mani, Mesfin Fanta, Nicolas Hoch, Michael Weinfeld, Keith W Caldecott
The scaffold protein X-ray repair cross-complementing 1 (XRCC1) interacts with multiple enzymes involved in DNA base excision repair and single-strand break repair (SSBR) and is important for genetic integrity and normal neurological function. One of the most important interactions of XRCC1 is that with polynucleotide kinase/phosphatase (PNKP), a dual-function DNA kinase/phosphatase that processes damaged DNA termini and that, if mutated, results in ataxia with oculomotor apraxia 4 (AOA4) and microcephaly with early-onset seizures and developmental delay (MCSZ)...
August 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28820895/identification-of-leishmania-donovani-antigen-in-circulating-immune-complexes-of-visceral-leishmaniasis-subjects-for-diagnosis
#3
Fauzia Jamal, Pushkar Shivam, Sarita Kumari, Manish Kumar Singh, Abul Hasan Sardar, Pushpanjali, Selvasankar Murugesan, Shyam Narayan, Anil Kumar Gupta, Krishna Pandey, V N R Das, Vahab Ali, Sanjiva Bimal, Pradeep Das, Shubhankar K Singh
The unreliability of most of the existing antibody-based diagnostic kits to discriminate between active and treated VL cases, relapse situation and reinfection are a major hurdle in controlling the cases of Kala-azar in an endemic area. An antigen targeted diagnostic approaches can be an attractive strategy to overcome these problems. Hence, this study was focused on identifying the Leishmania antigens, lies in circulating immune complex (CICs), can be used for diagnostic as well as prognostic purposes. The present study was conducted on peripheral blood samples of 115 human subjects, based on isolation of CICs...
2017: PloS One
https://www.readbyqxmd.com/read/28820292/p53-binding-sites-in-normal-and-cancer-cells-are-characterized-by-distinct-chromatin-context
#4
Feifei Bao, Peter R LoVerso, Jeffrey N Fisk, Victor B Zhurkin, Feng Cui
The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed two distinct epigenetic features underlying p53-DNA interactions in vivo...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28819659/solvent-hydrophobicity-induced-complex-coacervation-of-dsdna-and-in-situ-formed-zein-nanoparticles
#5
Pankaj Kumar Pandey, Priyanka Kaushik, Kamla Rawat, V K Aswal, H B Bohidar
Zein, a predominantly hydrophobic protein, was sustained as a stable dispersion in ethanol-water (80 : 20, % (v/v)) binary solvent at room temperature (25 °C). Addition of aqueous dsDNA solution (1% (w/v)) to the above dispersion prepared with the protein concentration of Czein = 0.01-0.5% (w/v) caused a concomitant change in ethanol content from 14-35% (v/v), which in turn generated zein nanoparticles in situ of size 80-120 nm increasing with water content. The subsequent associative interaction between DNA (polyanion; 2000 bps) and the positively charged zein nanoparticles, (at pH = 4) was driven by Coulombic forces, and by the solvent hydrophobicity due to the ethanol content of the binary solvent...
August 18, 2017: Soft Matter
https://www.readbyqxmd.com/read/28819300/yebc-a-putative-transcriptional-factor-involved-in-the-regulation-of-the-proteolytic-system-of-lactobacillus
#6
Lucía Brown, Josefina M Villegas, Mariano Elean, Silvina Fadda, Fernanda Mozzi, Lucila Saavedra, Elvira M Hebert
The proteolytic system of Lactobacillus plays an essential role in bacterial growth, contributes to the flavor development of fermented products, and can release bioactive health-beneficial peptides during milk fermentation. In this work, a genomic analysis of all genes involved in the proteolytic system of L. delbrueckii subsp. lactis CRL 581 was performed. Genes encoding the cell envelope-associated proteinase, two peptide transport systems, and sixteen peptidases were identified. The influence of the peptide supply on the transcription of 23 genes involved in the proteolytic system of L...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819200/periostin-binding-dna-aptamer-treatment-attenuates-renal-fibrosis-under-diabetic-conditions
#7
Jae Eun Um, Jung Tak Park, Bo Young Nam, Jung Pyo Lee, Jong Ha Jung, Youndong Kim, Seonghun Kim, Jimin Park, Meiyan Wu, Seung Hyeok Han, Tae-Hyun Yoo, Shin-Wook Kang
Diabetic nephropathy, the major cause of chronic kidney disease, is associated with progressive renal fibrosis. Recently, accumulation of periostin, an extracellular matrix protein, was shown to augment renal fibrosis. Aptamers have higher binding affinities without developing the common side effects of antibodies. Thus, we evaluated the effect of periostin inhibition by an aptamer-based inhibitor on renal fibrosis under diabetic conditions. In vitro, transforming growth factor-β1 (TGF-β1) treatment significantly upregulated periostin, fibronectin, and type I collagen mRNA and protein expressions in inner medullary collecting duct (IMCD) cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819114/isothermal-amplification-of-long-discrete-dna-fragments-facilitated-by-single-stranded-binding-protein
#8
Yinhua Zhang, Nathan A Tanner
Isothermal amplification methods for detection of DNA and RNA targets have expanded significantly in recent years, promising a new wave of simple and rapid molecular diagnostics. Current isothermal methods result in the generation of short fragments (<150 base pairs) or highly branched long DNA products. Here we report the amplification of discrete target fragments of several kilobases at 37 °C from both double- and single-stranded circular template DNA using specific primer pairs. In contrast to existing methods, this amplification requires only the single-stranded DNA-binding protein gp32 from bacteriophage T4 and a strand-displacing DNA polymerase...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818726/identification-of-functional-interactome-of-a-key-cell-division-regulatory-protein-ceda-of-e-coli
#9
Pankaj Sharma, Anil Kumar Tomar, Bishwajit Kundu
Cell division is compromised in DnaAcos mutant Escherichia coli cells that results in filamentous cell morphology. This is countered by over-expression of CedA protein that induces cytokinesis and thus, regular cell morphology is regained; however via an unknown mechanism. To understand the process systematically, exact role of CedA should be deciphered. Protein interactions are crucial for functional organization of a cell and their identification helps in revealing exact function(s) of a protein and its binding partners...
August 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28818672/glutathione-monoethyl-ester-prevents-tdp-43-pathology-in-motor-neuronal-nsc-34%C3%A2-cells
#10
Tong Chen, Bradley J Turner, Philip M Beart, Lucy Sheehan-Hennessy, Chinasom Elekwachi, Hakan Muyderman
Oxidative stress is recognised as central in a range of neurological diseases including Amyotrophic lateral sclerosis (ALS), a disease characterised by fast progressing death of motor neurons in the brain and spinal cord. Cellular pathology includes cytosolic protein aggregates in motor neurons and glia of which potentially cytotoxic hyper-phosphorylated fragments of the Transactive response DNA Binding Protein 43 kDa (TDP-43) constitute a major component. This is closely associated with an additional loss of nuclear TDP-43 expression indicating a "loss of function" mechanism, accelerating motor neuron (MN) loss...
August 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28818101/a-new-method-for-sequencing-the-hypervariable-plasmodium-falciparum-gene-var2csa-from-clinical-samples
#11
Antoine Dara, Mark A Travassos, Matthew Adams, Sarah Schaffer DeRoo, Elliott F Drábek, Sonia Agrawal, Miriam K Laufer, Christopher V Plowe, Joana C Silva
BACKGROUND: VAR2CSA, a member of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, mediates the binding of P. falciparum-infected erythrocytes to chondroitin sulfate A, a surface-associated molecule expressed in placental cells, and plays a central role in the pathogenesis of placental malaria. VAR2CSA is a target of naturally acquired immunity and, as such, is a leading vaccine candidate against placental malaria. This protein is very polymorphic and technically challenging to sequence...
August 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28817800/tia1-mutations-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-promote-phase-separation-and-alter-stress-granule-dynamics
#12
Ian R Mackenzie, Alexandra M Nicholson, Mohona Sarkar, James Messing, Maria D Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B Perkerson, Aishe Kurti, Billie J Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R Hsiung, Charles Krieger, Melissa E Murray, Masato Kato, John D Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A Zivkovic, Veronica Hirsch-Reinshagen, Raymond P Roos, Stephan Züchner, Neill R Graff-Radford, Ronald C Petersen, Richard J Caselli, Zbigniew K Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B Boylan, J Paul Taylor, Rosa Rademakers
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10(-6)). Postmortem neuropathology of five TIA1 mutations carriers showed a consistent pathological signature with numerous round, hyaline, TAR DNA-binding protein 43 (TDP-43)-positive inclusions...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28817778/the-oxidation-state-of-4fe4s-clusters-modulates-the-dna-binding-affinity-of-dna-repair-proteins
#13
Edmund C M Tse, Theodore J Zwang, Jacqueline K Barton
A central question important to understanding DNA repair is how certain proteins are able to search for, detect, and fix DNA damage on a biologically relevant timescale. A feature of many base excision repair proteins is that they contain [4Fe4S] clusters that may aid their search for lesions. In this report, we establish the importance of the oxidation state of the redox-active [4Fe4S] cluster in the DNA damage detection process. We utilize DNA-modified electrodes to generate repair proteins with [4Fe4S] clusters in the 2+ and 3+ states by bulk electrolysis under an O2-free atmosphere...
August 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28817112/monoallelic-and-biallelic-creb3l1-variant-causes-mild-and-severe-osteogenesis-imperfecta-respectively
#14
Rachel B Keller, Thao T Tran, Shawna M Pyott, Melanie G Pepin, Ravi Savarirayan, George McGillivray, Deborah A Nickerson, Michael J Bamshad, Peter H Byers
PurposeOsteogenesis imperfecta (OI) is a heritable skeletal dysplasia. Dominant pathogenic variants in COL1A1 and COL1A2 explain the majority of OI cases. At least 15 additional genes have been identified, but those still do not account for all OI phenotypes that present. We sought the genetic cause of mild and lethal OI phenotypes in an unsolved family.MethodsWe performed exome sequencing on seven members of the family, both affected and unaffected.ResultsWe identified a variant in cyclic AMP responsive element binding protein 3-like 1 (CREB3L1) in a consanguineous family...
August 17, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28815851/basics-of-genome-editing-technology-and-its-application-in-livestock-species
#15
REVIEW
Bjoern Petersen
In the last decade, the research community has witnessed a blooming of targeted genome editing tools and applications. Novel programmable DNA nucleases such as zinc finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs) and the clustered regularly interspaced short palindromic repeats/Cas9 system (CRISPR/Cas9) possess long recognition sites and are capable of cutting DNA in a very specific manner. These DNA nucleases mediate targeted genetic alterations by enhancing the DNA mutation rate via induction of double-strand breaks at a predetermined genomic site...
August 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28815832/targeting-the-genome-stability-hub-ctf4-by-stapled-peptide-design
#16
Yuteng Wu, Fabrizio Villa, Joseph Maman, Lina Dobnikar, Yu H Lau, Aline C Simon, Karim Labib, David R Spring, Luca Pellegrini
Exploitation of synthetic lethality by small-molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND-1 protein hub that links DNA replication, repair and chromosome segregation, represents a novel target for the synthetic lethality approach. Here we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. Screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, sub-micromolar binding to Ctf4...
August 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28814948/synthesis-characterization-cytotoxic-activity-and-interactions-with-ct-dna-and-bsa-of-cationic-ruthenium-ii-complexes-containing-dppm-and-quinoline-carboxylates
#17
Edinaldo N da Silva, Paulo A B da Silva, Angélica E Graminha, Pollyanna F de Oliveira, Jaqueline L Damasceno, Denise C Tavares, Alzir A Batista, Gustavo Von Poelhsitz
The complexes cis-[Ru(quin)(dppm)2]PF6 and cis-[Ru(kynu)(dppm)2]PF6 (quin = quinaldate; kynu = kynurenate; dppm = bis(diphenylphosphino)methane) were prepared and characterized by elemental analysis, electronic, FTIR, (1)H, and (31)P{(1)H} NMR spectroscopies. Characterization data were consistent with a cis arrangement for the dppm ligands and a bidentate coordination through carboxylate oxygens of the quin and kynu anions. These complexes were not able to intercalate CT-DNA as shown by circular dichroism spectroscopy...
2017: Bioinorganic Chemistry and Applications
https://www.readbyqxmd.com/read/28814752/oncofetal-hmga2-effectively-curbs-unconstrained-and-dna-supercoiling
#18
Xiaodan Zhao, Sabrina Peter, Peter Dröge, Jie Yan
HMGA2 belongs to the family of the high mobility group (HMG) proteins. It binds DNA via three AT-hook domains to the minor groove of adenine-thymine (AT) rich DNA. Recently, a new function of HMGA2 as a replication fork chaperone that protects stem and cancer cells from replication fork collapse induced by chemotherapeutic agents was uncovered, suggesting a previously uncharacterized binding at replication forks. In this study, we examined HMGA2 binding to four DNA structures relevant to replication forks, namely ds DNA, ss DNA, forked DNA and supercoiled DNA plectonemes...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#19
Su Jung Bae, Hye Joo Kim, Hee Yeon Won, Yong Ki Min, Eun Sook Hwang
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814300/increasing-on-target-cleavage-efficiency-for-crispr-cas9-induced-large-fragment-deletion-in-myxococcus-xanthus
#20
Ying-Jie Yang, Ye Wang, Zhi-Feng Li, Ya Gong, Peng Zhang, Wen-Chao Hu, Duo-Hong Sheng, Yue-Zhong Li
BACKGROUND: The CRISPR/Cas9 system is a powerful tool for genome editing, in which the sgRNA binds and guides the Cas9 protein for the sequence-specific cleavage. The protocol is employable in different organisms, but is often limited by cell damage due to the endonuclease activity of the introduced Cas9 and the potential off-target DNA cleavage from incorrect guide by the 20 nt spacer. RESULTS: In this study, after resolving some critical limits, we have established an efficient CRISPR/Cas9 system for the deletion of large genome fragments related to the biosynthesis of secondary metabolites in Myxococcus xanthus cells...
August 16, 2017: Microbial Cell Factories
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