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https://www.readbyqxmd.com/read/28531304/replication-studies-of-carboxymethylated-dna-lesions-in-human-cells
#1
Jun Wu, Pengcheng Wang, Lin Li, Nicole L Williams, Debin Ji, Walter J Zahurancik, Changjun You, Jianshuang Wang, Zucai Suo, Yinsheng Wang
Metabolic activation of some N-nitroso compounds (NOCs), an important class of DNA damaging agents, can induce the carboxymethylation of nucleobases in DNA. Very little was previously known about how the carboxymethylated DNA lesions perturb DNA replication in human cells. Here, we investigated the effects of five carboxymethylated DNA lesions, i.e. O6-CMdG, N6-CMdA, N4-CMdC, N3-CMdT and O4-CMdT on the efficiency and fidelity of DNA replication in HEK293T human embryonic kidney cells. We found that, while neither N6-CMdA nor N4-CMdC blocked DNA replication or induced mutations, N3-CMdT, O4-CMdT and O6-CMdG moderately blocked DNA replication and induced substantial frequencies of T→A (81%), T→C (68%) and G→A (6...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28530384/divalent-metal-ion-activation-of-a-guanine-general-base-in-the-hammerhead-ribozyme-insights-from-molecular-simulations
#2
Haoyuan Chen, Timothy J Giese, Barbara L Golden, Darrin M York
The hammerhead ribozyme is a well-studied nucleolytic ribozyme that catalyzes the self-cleavage of the RNA phosphodiester backbone. Despite experimental and theoretical efforts, there remain key questions about details of the mechanism with regard to the activation of the nucleophile by the putative general base guanine (G12). Straight-forward interpretation of the measured activity-pH data implies the pKa value of the N1 position in the G12 nucleobase is significantly shifted by the ribozyme environment. Recent crystallographic and biochemical work has identified pH-dependent divalent metal ion binding at the N7/O6 position of G12, leading to the hypothesis that this binding mode could induce a pKa shift of G12 towards neutrality...
May 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28529799/new-m-m-3-arsenates-the-framework-structures-of-agm-3-haso4-2-m-3-al-ga-and-m-gaas2o7-m-na-ag
#3
Karolina Schwendtner, Uwe Kolitsch
The crystal structures of hydro-thermally synthesized silver(I) aluminium bis-[hydrogen arsenate(V)], AgAl(HAsO4)2, silver(I) gallium bis-[hydrogen arsenate(V)], AgGa(HAsO4)2, silver gallium diarsenate(V), AgGaAs2O7, and sodium gallium diarsenate(V), NaGaAs2O7, were determined from single-crystal X-ray diffraction data collected at room temperature. The first two compounds are representatives of the MCV-3 structure type known for KSc(HAsO4)2, which is characterized by a three-dimensional anionic framework of corner-sharing alternating M(3+)O6 octa-hedra (M = Al, Ga) and singly protonated AsO4 tetra-hedra...
May 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28529131/the-structure-of-the-guanidine-ii-riboswitch
#4
Lin Huang, Jia Wang, David M J Lilley
The guanidine-II (mini-ykkC) riboswitch is the smallest of the guanidine-responsive riboswitches, comprising two stem loops of similar sequence. We have solved high-resolution crystal structures of both stem loops for the riboswitch from Gloeobacter violaceus. The stem loops have a strong propensity to dimerize by intimate loop-loop interaction. The dimerization creates specific binding pockets for two guanidine molecules, explaining their cooperative binding. Within the binding pockets the ligands are hydrogen bonded to a guanine at O6 and N7, and to successive backbone phosphates...
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28506525/how-does-mg-2-modulate-the-rna-folding-mechanism-a-case-study-of-the-g-c-w-w-trans-basepair
#5
Antarip Halder, Rohit Roy, Dhananjay Bhattacharyya, Abhijit Mitra
Reverse Watson-Crick G:C basepairs (G:C W:W Trans) occur frequently in different functional RNAs. This is one of the few basepairs whose gas-phase-optimized isolated geometry is inconsistent with the corresponding experimental geometry. Several earlier studies indicate that through post-transcriptional modification, direct protonation, or coordination with Mg(2+), accumulation of positive charge near N7 of guanine can stabilize the experimental geometry. Interestingly, recent studies reveal significant variation in the position of putatively bound Mg(2+)...
May 12, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28481096/cuo-and-zno-nanoparticles-modify-interkingdom-cell-signaling-processes-relevant-to-crop-production-a-review
#6
Anne Anderson, Joan E McLean, Astrid Rosa Jacobson, David Britt
As the world population increases, strategies for sustainable agriculture are needed to fulfill the global need for plants for food and other commercial products. Nanoparticle formulations are likely to be part of the developing strategies. CuO and ZnO nanoparticles (NPs) offer potential as fertilizers, as they provide bioavailable essential metals, and as pesticides, because of dose-dependent toxicity. Effects of these metal oxide NPs on rhizosphere functions are the focus of this review. These NPs at doses of 10 mg metal/kg and above change production of key metabolites involved in plant protection in a root-associated microbe, Pseudomonas chlororaphis O6...
May 8, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28460122/transcriptional-mutagenesis-reduces-splicing-fidelity-in-mammalian-cells
#7
João A Paredes, Monika Ezerskyte, Matteo Bottai, Kristian Dreij
Splicing fidelity is essential to the maintenance of cellular functions and viability, and mutations or natural variations in pre-mRNA sequences and consequent alteration of splicing have been implicated in the etiology and progression of numerous diseases. The extent to which transcriptional errors or lesion-induced transcriptional mutagenesis (TM) influences splicing fidelity is not currently known. To investigate this, we employed site-specific DNA lesions on the transcribed strand of a minigene splicing reporter in normal mammalian cells...
April 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28453749/an-independently-validated-nomogram-for-individualized-estimation-of-survival-among-patients-with-newly-diagnosed-glioblastoma-nrg-oncology-rtog-0525-and-0825
#8
Haley Gittleman, Daniel Lim, Michael W Kattan, Arnab Chakravarti, Mark R Gilbert, Andrew B Lassman, Simon S Lo, Mitchell Machtay, Andrew E Sloan, Erik P Sulman, Devin Tian, Michael A Vogelbaum, Tony J C Wang, Marta Penas-Prado, Emad Youssef, Deborah T Blumenthal, Peixin Zhang, Minesh P Mehta, Jill S Barnholtz-Sloan
Background.: Glioblastoma (GBM) is the most common primary malignant brain tumor. Nomograms are often used for individualized estimation of prognosis. This study aimed to build and independently validate a nomogram to estimate individualized survival probabilities for patients with newly diagnosed GBM, using data from 2 independent NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. Methods.: This analysis included information on 799 (RTOG 0525) and 555 (RTOG 0825) eligible and randomized patients with newly diagnosed GBM and contained the following variables: age at diagnosis, race, gender, Karnofsky performance status (KPS), extent of resection, O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and survival (in months)...
May 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28453281/designing-ligands-to-isolate-znln-and-zn2ln-complexes-field-induced-single-ion-magnet-behavior-of-the-zndy-zn2dy-and-zn2er-analogues
#9
Matilde Fondo, Julio Corredoira-Vázquez, Ana M García-Deibe, Jesús Sanmartín-Matalobos, Juan Manuel Herrera, Enrique Colacio
A new H3L Schiff base ligand with three defined compartments, namely, two internal NNO and one external O6, was designed to allocate metal ions of different size. This ligand allows isolating heterodinuclear [ZnLn(HL)(NO3)(OAc)(D)](NO3) (Ln = Tb, D = H2O, ZnTb; Ln = Dy, D = CH3OH, ZnDy; and Ln = Er, D = CH3OH, ZnEr) complexes, where one of the NNO pockets allocates a zinc(II) ion, while the other one is empty, or heterotrinuclear [Zn2Ln(L)(NO3)2(OAc)2(H2O)] (Ln = Dy, Zn2Dy and Ln = Er, Zn2Er) compounds, where each NNO compartment accommodates Zn(II)...
April 28, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28443888/sugar-peptidic-bond-interactions-spectroscopic-characterization-of-a-model-system
#10
Ander Camiruaga, Imanol Usabiaga, Aran Insausti, Iker León, José A Fernández
Sugars are small carbohydrates which play numerous roles in living organisms such as storage of energy or as structural components. Modifications of specific sites within the glycan chain can modulate a carbohydrate's overall biological function as it happens with nucleic acids and proteins. Hence, identifying discrete carbohydrate modifications and understanding their biological effects is essential. A study of such processes requires of a deep knowledge of the interaction mechanism at the molecular level...
May 17, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28436299/mgmt-gene-variants-temozolomide-myelotoxicity-and-glioma-risk-a-concise-literature-survey-including-an-illustrative-case
#11
Meric A Altinoz, Ilhan Elmaci, Fatih Han Bolukbasi, Cumhur Gokhan Ekmekci, Guven Yenmis, Ramazan Sari, Aydin Sav
Temozolomide may cause thrombocytopenia or neutropenia in 3-4% of glioblastoma patients, respectively. However, pancytopenia is rarely reported. MGMT (O6-methylguanine-DNA-methyltransferase) enzyme repairs temozolomide-induced DNA mutations and associates both with antitumour efficacy and myelosuppression. Many studies on the effects of MGMT gene-methylation on temozolomide's effects exist, but much fewer publications concerning MGMT variants were documented. A full sequencing of the MGMT gene was performed in a female glioblastoma patient, who developed pancytopenia following temozolomide treatment...
April 23, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28429715/mapping-clinicopathological-entities-within-colorectal-mucinous-adenocarcinomas-a-hierarchical-clustering-approach
#12
Charly Liddell, Laure Droy-Dupré, Sylvie Métairie, Fabrice Airaud, Christelle Volteau, Stéphane Bezieau, Christian L Laboisse, Jean-François Mosnier
The aim of this study was to interrogate the heterogeneity of colorectal mucinous adenocarcinomas. This study is based on hierarchical clustering approach combining clinicopathological and molecular patterns known to be relevant to oncogenesis and therapeutic management of patients with colorectal carcinoma, ie, microsatellite instability, O6-methylguanine-DNA methyltransferase (MGMT) status, KRAS, and BRAF mutations and wnt signaling pathway activation. Comparison of the study group of 60 mucinous adenocarcinomas defined according to World Health Organization classification with control group of 136 colorectal adenocarcinomas successively removed shows higher frequency of BRAF and KRAS mutations and microsatellite instability-high status and lower frequency of wnt signaling pathway activation in mucinous adenocarcinomas...
April 21, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28427986/prognostic-implications-of-extent-of-resection-in-glioblastoma-analysis-from-a-large-database
#13
Daniel M Trifiletti, Clayton Alonso, Surbhi Grover, Camilo E Fadul, Jason P Sheehan, Timothy N Showalter
OBJECTIVE: To analyze the predictors for and clinical impact of gross total resection (GTR) in patients with glioblastoma (GBM). METHODS AND MATERIALS: The National Cancer Database was queried for patients with GBM diagnosed from 2004-2013 with known survival and extent of resection. Patients were grouped based on extent of resection into biopsy alone, subtotal resection (STR), and GTR. Univariable and multivariable (MVA) analyses were performed to investigate factors associated with the likelihood of GTR and overall survival (OS) following diagnosis...
April 17, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28427088/a-phase-2-study-of-temozolomide-in-pretreated-metastatic-colorectal-cancer-with-mgmt-promoter-methylation
#14
M A Calegari, A Inno, S Monterisi, A Orlandi, D Santini, M Basso, A Cassano, M Martini, T Cenci, I de Pascalis, F Camarda, B Barbaro, L M Larocca, S Gori, G Tonini, C Barone
BACKGROUND: Presently, few options are available for refractory colorectal cancer (CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a frequent and early event in CRC tumourigenesis. This epigenetic silencing is a predictor of response to the alkylating drug temozolomide in glioblastoma. Preclinical evidences and some case reports showed temozolomide activity in CRC with MGMT silencing, but the available data from clinical trials are inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according to a two-stage Simon's optimal design to investigate activity and safety of temozolomide in refractory CRC harbouring MGMT promoter methylation...
May 9, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28415741/enhancement-of-radiosensitivity-by-the-novel-anticancer-quinolone-derivative-vosaroxin-in-preclinical-glioblastoma-models
#15
Giovanni Luca Gravina, Andrea Mancini, Claudia Mattei, Flora Vitale, Francesco Marampon, Alessandro Colapietro, Giulia Rossi, Luca Ventura, Antonella Vetuschi, Ernesto Di Cesare, Judith A Fox, Claudio Festuccia
PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). RESULTS: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405827/mgmt-promoter-methylation-status-in-merkel-cell-carcinoma-in-vitro-versus-invivo
#16
Giuseppina Improta, Cathrin Ritter, Angela Pettinato, Valeria Vasta, David Schrama, Filippo Fraggetta, Jürgen C Becker
PURPOSE: Expression of O6-methylguanine-DNA methyltransferase (MGMT) in Merkel cell carcinoma (MCC) is very variable; thus, we tested whether this may be due to differential methylation of the MGMT gene promoter. METHODS: Quantitative analysis of MGMT mRNA and protein expression, as well as MGMT promoter methylation status, was performed in a series of tissue samples of MCC tumors, representing both primary and metastatic lesions, as well as in six MCC cell lines...
April 12, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28395138/formation-of-s-2-n-6-deoxyadenosinyl-ethyl-glutathione-in-dna-and-replication-past-the-adduct-by-translesion-dna-polymerases
#17
Carl A Sedgeman, Yan Su, F Peter Guengerich
1,2-Dibromoethane (DBE, ethylene dibromide) is a potent carcinogen due at least in part to its DNA cross-linking effects. DBE cross-links glutathione (GSH) to DNA, notably to sites on 2'-deoxyadenosine and 2'-deoxyguanosine ( Cmarik , J. L. , et al. ( 1991 ) J. Biol. Chem. 267 , 6672 - 6679 ). Adduction at the N6 position of 2'-deoxyadenosine (dA) had not been detected, but this is a site for the linkage of O(6)-alkylguanine DNA alkyltransferase ( Chowdhury , G. , et al. ( 2013 ) Angew. Chem. Int. Ed. 52 , 12879 - 12882 )...
April 14, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28389881/influence-of-incidental-radiation-dose-in-the-subventricular-zone-on-survival-in-patients-with-glioblastoma-multiforme-treated-with-surgery-radiotherapy-and-temozolomide
#18
P Foro Arnalot, O Pera, N Rodriguez, X Sanz, A Reig, I Membrive, A Ortiz, R Granados, M Algara
PURPOSE: To determine if there is an association between the incidental radiation dose to the subventricular zone and survival in patients with glioblastoma multiforme treated with surgery, radiotherapy and temozolomide. METHODS AND MATERIALS: Sixty-five patients, treated between 2006 and 2015, were included in this retrospective study. The doses (75th percentile; p75) administered to the ipsilateral, contralateral and bilateral subventricular zone were compared to overall survival and progression-free survival using Cox proportional hazards models...
April 7, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28367443/electrostatic-switch-function-in-the-mechanism-of-protein-kinase-a-i%C3%AE-activation-results-of-the-molecular-dynamics-simulation
#19
Olga N Rogacheva, Boris F Shchegolev, Elena A Vershinina, Alexander A Tokmakov, Vasiliy E Stefanov
We used molecular dynamics to find the average path of the A-domain H → B conformational transition in protein kinase A Iα. We obtained thirteen productive trajectories and processed them sequentially using factor and cross-correlation analyses. The conformational transition is presented as partly deterministic sequence of six events. Event B represents H → B transition of the phosphate binding cassette. Main participants of this event form electrostatic switch cAMP(O6)-A202(N-H)-G199(C=O). Through this switch, cAMP transmits information about its binding to hydrophobic switch L203-Y229 and thus triggers conformational transition of A-domain...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28355483/gas-phase-conformations-and-n-glycosidic-bond-stabilities-of-sodium-cationized-2-deoxyguanosine-and-guanosine-sodium-cations-preferentially-bind-to-the-guanine-residue
#20
Y Zhu, L A Hamlow, C C He, J K Lee, J Gao, G Berden, J Oomens, M T Rodgers
2'-Deoxyguanosine (dGuo) and guanosine (Guo) are fundamental building blocks of DNA and RNA nucleic acids. In order to understand the effects of sodium cationization on the gas-phase conformations and stabilities of dGuo and Guo, infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and complementary electronic structure calculations are performed. The measured IRMPD spectra of [dGuo+Na](+) and [Guo+Na](+) are compared to calculated IR spectra predicted for the stable low-energy structures computed for these species to determine the most favorable sodium cation binding sites, identify the structures populated in the experiments, and elucidate the influence of the 2'-hydroxyl substituent on the structures and IRMPD spectral features...
April 11, 2017: Journal of Physical Chemistry. B
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