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https://www.readbyqxmd.com/read/29149411/elusive-role-of-tctp-protein-and-mrna-in-cell-cycle-and-cytoskeleton-regulation
#1
Jacek Z Kubiak, Malgorzata Kloc
Translationally Controlled Tumor-associated Protein (TCTP) is a small, 23 kDa multifunctional and ubiquitous protein localized both in the cytoplasm and in the nucleus of eukaryotic cells. It is evolutionarily highly conserved. Certain aspects of its structure show remarkable similarities to guanine nucleotide-free chaperons Mss4 and Dss4 suggesting that at least some functions of TCTP may depend on its chaperon-like action on other proteins. Besides other functions, TCTP is clearly involved in cell cycle regulation...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29148817/specific-recognition-of-g-quadruplexes-over-duplex-dna-by-a-macromolecular-nir-two-photon-fluorescent-probe
#2
Marco Deiana, Bastien Mettra, Lara Martinez-Fernandez, Leszek Mateusz Mazur, Krzysztof Pawlik, Chantal Andraud, Marek Samoc, Roberto Improta, Cyrille Monnereau, Katarzyna Matczyszyn
The implication of guanine-rich DNA sequences in biologically important roles such as telomerase dysfunction and the regulation of gene expression has prompted the search for structure-specific G-quadruplex agents for targeted diagnostic and therapeutic applications. To date, the number of two-photon absorbing fluorogenic dyes with intrinsically large two-photon absorption (TPA) cross-section (σ2) and quantum yield (φf), capable of specific detection of G-motifs over duplex DNAs is still limited. Herein, we report on a NIR two-photon poly(cationic) anthracene-based macromolecule able to selectively target G-quadruplexes (G4s) over genomic double-stranded DNA...
November 17, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/29148771/an-qm-mm-study-of-the-reaction-catalyzed-by-alkyladenine-dna-glycosylase-examination-of-the-substrate-specificity-of-a-dna-repair-enzyme
#3
Stefan A P Lenz, Stacey D Wetmore
Human alkyladenine DNA glycosylase (AAG) functions as part of the base excision repair pathway to excise structurally diverse oxidized and alkylated DNA purines. Specifically, AAG uses a water molecule activated by a general base and a non-specific active site lined with aromatic residues to cleave the N-glycosidic bond. Despite broad substrate specificity, AAG does not target the natural purines (adenine (A) and guanine (G)). Using the ONIOM(QM:MM) methodology, we provide fundamental atomic level details of AAG bound to DNA-containing a neutral substrate (hypoxanthine (Hx)), a non-substrate (G), or a cationic substrate (7-methylguanine (7MeG)), and probe changes in the reaction pathway that occur when AAG targets different nucleotides...
November 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29147531/catalysis-of-a-1-3-dipolar-reaction-by-distorted-dna-incorporating-a-heterobimetallic-platinum-ii-and-copper-ii-complex
#4
Iván Rivilla, Abel de Cózar, Thomas Schäfer, Frank J Hernandez, Alexander M Bittner, Aitziber Eleta-Lopez, Ali Aboudzadeh, José I Santos, José I Miranda, Fernando P Cossío
A novel catalytic system based on covalently modified DNA is described. This catalyst promotes 1,3-dipolar reactions between azomethine ylides and maleimides. The catalytic system is based on the distortion of the double helix of DNA by means of the formation of Pt(ii) adducts with guanine units. This distortion, similar to that generated in the interaction of DNA with platinum chemotherapeutic drugs, generates active sites that can accommodate N-metallated azomethine ylides. The proposed reaction mechanism, based on QM(DFT)/MM calculations, is compatible with thermally allowed concerted (but asynchronous) [π4s + π2s] mechanisms leading to the exclusive formation of racemic endo-cycloadducts...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29145502/hi-fidelity-discrimination-of-isomirs-using-g-quadruplex-gatekeepers
#5
Nianjia Seow, Renzo A Fenati, Ashley R Connolly, Amanda V Ellis
Core microRNA (miRNA) sequences exist as populations of variants called isomiRs made up of different lengths and nucleotide compositions. In particular, the short sequences of miRNA make single-base isomiR mismatches very difficult to be discriminated. Non-specific hybridizations often arise when DNA probe-miRNA target hybridization is the primary, or initial, mode of detection. These errors then become exacerbated through subsequent amplification steps. Here, we present the design of DNA probes modified with poly-guanine (PG) tracts that were induced to form G-quadruplexes (G4) for hi-fidelity discrimination of miRNA core target sequence from single-base mismatched isomiRs...
2017: PloS One
https://www.readbyqxmd.com/read/29145128/microgravity-simulation-activates-cdc42-via-rap1gds1-to-promote-vascular-branch-morphogenesis-during-vasculogenesis
#6
Shouli Wang, Zhao Yin, Bei Zhao, Yanmei Qi, Jie Liu, Saum A Rahimi, Leonard Y Lee, Shaohua Li
Gravity plays an important role in normal tissue maintenance. The ability of stem cells to repair tissue loss in space through regeneration and differentiation remains largely unknown. To investigate the impact of microgravity on blood vessel formation from pluripotent stem cells, we employed the embryoid body (EB) model for vasculogenesis and simulated microgravity by clinorotation. We first differentiated mouse embryonic stem cells into cystic EBs containing two germ layers and then analyzed vessel formation under clinorotation...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29144554/a-sensitive-colorimetric-dna-biosensor-for-specific-detection-of-the-hbv-gene-based-on-silver-coated-glass-slide-and-g-quadruplex-hemin-dnazyme
#7
Yubin Li, Sheng Liu, Qiujuan Deng, Liansheng Ling
A sensitive colorimetric DNA biosensor for specific detection of single stranded oligonucleotide (ssDNA) is proposed in this paper. The biosensor is based on silver-coated glass (SCGS) and G-quadruplex-hemin DNAzyme. Capture DNA is immobilized on the surface of SCGS by Ag-S bond. Signal DNA can be used to hybridize with the target DNA which is selected from the Hepatitis B virus(HBV) gene as target HBV DNA, and the HRP-mimicking G-quadruplex-hemin DNAzyme can be formed through the function of a guanine-rich fragment from signal DNA to catalyze the oxidation of 2,2-azinobis(3-ethylbenzothiozoline)-6-sulfonicacid (ABTS(2-) ) by H2 O2 ...
November 16, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/29144399/dna-g-wire-formation-using-an-artificial-peptide-is-controlled-by-protease-activity
#8
Kenji Usui, Arisa Okada, Shungo Sakashita, Masayuki Shimooka, Takaaki Tsuruoka, Shu-Ichi Nakano, Daisuke Miyoshi, Tsukasa Mashima, Masato Katahira, Yoshio Hamada
The development of a switching system for guanine nanowire (G-wire) formation by external signals is important for nanobiotechnological applications. Here, we demonstrate a DNA nanostructural switch (G-wire <--> particles) using a designed peptide and a protease. The peptide consists of a PNA sequence for inducing DNA to form DNA-PNA hybrid G-quadruplex structures, and a protease substrate sequence acting as a switching module that is dependent on the activity of a particular protease. Micro-scale analyses via TEM and AFM showed that G-rich DNA alone forms G-wires in the presence of Ca(2+), and that the peptide disrupted this formation, resulting in the formation of particles...
November 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29141659/rescue-of-high-specificity-cas9-variants-using-sgrnas-with-matched-5-nucleotides
#9
Sojung Kim, Taegeun Bae, Jaewoong Hwang, Jin-Soo Kim
We report that engineered Cas9 variants with improved specificity-eCas9-1.1 and Cas9-HF1-are often poorly active in human cells, when complexed with single guide RNAs (sgRNAs) with a mismatch at the 5' terminus, relative to target DNA sequences. Because the nucleotide at the 5' end of sgRNAs, expressed under the control of the commonly-used U6 promoter, is fixed to a guanine, these attenuated Cas9 variants are not useful at many target sites. By using sgRNAs with matched 5' nucleotides, produced by linking them to a self-cleaving ribozyme, the editing activity of Cas9 variants can be rescued without sacrificing high specificity...
November 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/29139578/structure-property-relationships-in-cuii-binding-tetramolecular-g-quadruplex-dna
#10
David M Engelhard, Lukas M Stratmann, Guido H Clever
A series of artificial metal-base tetrads composed of a CuII cation coordinating to four pyridines, covalently attached to the ends of tetramolecular G-quadruplex DNA strands [LA-Dd(G4)]4 (LA-D = ligand derivatives), was systematically studied. Structurally, the square-planar [Cu(pyridine)4] complex behaves analogous to the canonical guanine quartet. Copper coordination to all studied ligand derivatives was found to increase G-quadruplex thermodynamic stability, tolerating a great variety of ligand linker lengths (1 - 5 atoms) and thus demonstrating the robustness of the chosen ligand design...
November 15, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29137116/altering-residue-134-confers-an-increased-substrate-range-of-alkylated-nucleosides-to-the-e-coli-ogt-protein
#11
Nadia M Schoonhoven, Derek K O'Flaherty, Francis P McManus, Lauralicia Sacre, Anne M Noronha, M Judith Kornblatt, Christopher J Wilds
O⁶-Alkylguanine-DNA alkyltransferases (AGTs) are proteins responsible for the removal of mutagenic alkyl adducts at the O⁶-atom of guanine and O⁴-atom of thymine. In the current study we set out to understand the role of the Ser134 residue in the Escherichia coli AGT variant OGT on substrate discrimination. The S134P mutation in OGT increased the ability of the protein to repair both O⁶-adducts of guanine and O⁴-adducts of thymine. However, the S134P variant was unable, like wild-type OGT, to repair an interstrand cross-link (ICL) bridging two O⁶-atoms of guanine in a DNA duplex...
November 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29136793/electrochemical-monitoring-of-the-interaction-between-anticancer-drug-and-dna-in-the-presence-of-antioxidant
#12
Merve Muti, Mihrican Muti
The aim of this work is to find out the effect of antioxidant onto the interaction of DNA-anticancer drug, daunorubicin. Daunorubicin (DNR) is an anti-cancer drug which is used for the treatment of certain cancers including the treatment of leukemia. The treatments of patients, who suffer from cancer, become generally complicated if they take some antioxidant-containing supplement during chemotherapy. In this study, the interaction performance between DNR and DNA was investigated both in the presence and absence of antioxidant, caffeic acid, as the first time in the literature...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29136506/a-paradoxical-tumor-suppressor-role-for-the-rac1-exchange-factor-vav1-in-t-cell-acute-lymphoblastic-leukemia
#13
Javier Robles-Valero, L Francisco Lorenzo-Martín, Mauricio Menacho-Márquez, Isabel Fernández-Pisonero, Antonio Abad, Mireia Camós, María L Toribio, Lluis Espinosa, Anna Bigas, Xosé R Bustelo
Rho guanine exchange factors (GEFs), the enzymes that stimulate Rho GTPases, are deemed as potential therapeutic targets owing to their protumorigenic functions. However, the understanding of the spectrum of their pathobiological roles in tumors is still very limited. We report here that the GEF Vav1 unexpectedly possesses tumor-suppressor functions in immature T cells. This function entails the noncatalytic nucleation of complexes between the ubiquitin ligase Cbl-b and the intracellular domain of Notch1 (ICN1) that favors ICN1 ubiquitinylation and degradation...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136176/mutations-in-metg-methionyl-trna-synthetase-and-trmd-trna-guanine-n1-methyltransferase-conferring-meropenem-tolerance-in-burkholderia-thailandensis
#14
Hyojeong Yi, Hyeri Lee, Kwang-Hwi Cho, Heenam Stanley Kim
Objectives: Although meropenem is widely used to treat Burkholderia infections, the response of Burkholderia pathogens to this antibiotic is largely unexplored. Methods: Burkholderia thailandensis, a model for Burkholderia spp., particularly Burkholderia mallei and Burkholderia pseudomallei, was challenged with a lethal level of meropenem and survivors were isolated. The genomes of two of the isolates were analysed to identify mutated genes and these genes were then specifically examined in more isolates to profile mutation diversity...
November 9, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29133411/specific-inhibition-of-gpcr-independent-g-protein-signaling-by-a-rationally-engineered-protein
#15
Anthony Leyme, Arthur Marivin, Marcin Maziarz, Vincent DiGiacomo, Maria P Papakonstantinou, Prachi P Patel, Juan B Blanco-Canosa, Isha A Walawalkar, Gonzalo Rodriguez-Davila, Isabel Dominguez, Mikel Garcia-Marcos
Activation of heterotrimeric G proteins by cytoplasmic nonreceptor proteins is an alternative to the classical mechanism via G protein-coupled receptors (GPCRs). A subset of nonreceptor G protein activators is characterized by a conserved sequence named the Gα-binding and activating (GBA) motif, which confers guanine nucleotide exchange factor (GEF) activity in vitro and promotes G protein-dependent signaling in cells. GBA proteins have important roles in physiology and disease but remain greatly understudied...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29131588/kinetic-isotope-effects-and-transition-state-structure-for-hypoxanthine-guanine-xanthine-phosphoribosyltransferase-from-plasmodium-falciparum
#16
Rodrigo G Ducati, Ross S Firestone, Vern L Schramm
Plasmodium falciparum parasites are purine auxotrophs that rely exclusively on the salvage of preformed purines from their human hosts to supply the requirement for purine nucleotides. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) catalyzes the freely reversible Mg2+-dependent conversion of 6-oxopurine bases to their respective nucleotides and inorganic pyrophosphate. The phosphoribosyl group is derived from 5-phospho--D-ribosyl 1-pyrophosphate (PRPP). The enzyme from malaria parasites (PfHGXPRT) is essential as hypoxanthine is the major precursor in purine metabolism...
November 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/29131013/a-new-baltic-population-specific-human-genetic-marker-in-the-pmca4-gene
#17
Janis Stavusis, Inna Inashkina, Baiba Lace, Dita Pelnena, Svetlana Limborska, Andrey Khrunin, Vaidutis Kucinskas, Astrida Krumina, Linda Piekuse, Branko Zorn, Violeta Fodina, Margus Punab, Juris Erenpreiss
OBJECTIVES: The PMCA gene family consists of 4 genes and at least 21 splice variants; among these, the Ca2+ ATPase 4 (PMCA4) gene encodes a plasma membrane protein abundantly expressed in several tissues, including the kidney, heart, and sperm. Knockout of PMCA4 causes infertility due to immotile sperm in mouse models. We therefore investigated variants in this gene for potential association with infertility in groups of Estonian (n = 191) and Latvian (n = 92) men with reduced sperm motility...
November 2, 2017: Human Heredity
https://www.readbyqxmd.com/read/29130632/dock3-related-neurodevelopmental-syndrome-biallelic-intragenic-deletion-of-dock3-in-a-boy-with-developmental-delay-and-hypotonia
#18
Aiko Iwata-Otsubo, Alyssa L Ritter, Brooke Weckselbatt, Nicole R Ryan, David Burgess, Laura K Conlin, Kosuke Izumi
Dedicator of cytokinesis (DOCK) family are evolutionary conserved guanine nucleotide exchange factors (GEFs) for the Rho GTPases, Rac, and Cdc42. DOCK3 functions as a GEF for Rac1, and plays an important role in promoting neurite and axonal growth by stimulating actin dynamics and microtubule assembly pathways in the central nervous system. Here we report a boy with developmental delay, hypotonia, and ataxia due to biallelic DOCK3 deletion. Chromosomal single nucleotide polymorphism (SNP) microarray analysis detected a 170 kb homozygous deletion including exons 6-12 of the DOCK3 gene at 3p21...
November 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29127104/chemical-suppressors-of-mlo-mediated-powdery-mildew-resistance
#19
Hongpo Wu, Mark Kwaaitaal, Roxana Strugala, Ulrich Schaffrath, Pawel Bednarek, Ralph Panstruga
Loss of function of barley Mlo confers durable broad-spectrum penetration resistance to the barley powdery mildew pathogen , Blumeria graminis f. sp. hordei ( Bgh ). Given the importance of mlo mutants in agriculture, surprisingly few molecular components have been identified to be required for this type of resistance in barley. With the aim to identify novel cellular factors contributing to mlo -based resistance, we devised a pharmacological inhibitor screen. Of the 41 rationally chosen compounds tested, five caused a partial suppression of mlo resistance in barley, indicated by increased levels of Bgh host cell entry...
November 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29125988/quantification-of-nitrogenous-bases-dna-and-collagen-type-i-for-the-estimation-of-the-postmortem-interval-in-bone-remains
#20
Cristina Pérez-Martínez, María D Pérez-Cárceles, Isabel Legaz, Gemma Prieto-Bonete, Aurelio Luna
Estimating the postmortem interval (PMI) is an important goal in forensic medicine and continues to be one of the most difficult tasks of the forensic investigator. Few accurate methods exist to determine the time since death of skeletonized human remains due to the great number of intrinsic and external factors that may alter the normal course of postmortem change. The purpose of this research was to assess the usefulness of various biochemical parameters, such as nitrogenous bases (adenine, guanine, purines, cytosine, thymine, pyrimidines, hypoxanthine and xanthine), DNA and Collagen Type I peptides to estimate PMI...
November 4, 2017: Forensic Science International
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