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Ribonucleotide reductase

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https://www.readbyqxmd.com/read/28220209/s-phase-checkpoint-regulations-that-preserve-replication-and-chromosome-integrity-upon-dntp-depletion
#1
REVIEW
Michele Giannattasio, Dana Branzei
DNA replication stress, an important source of genomic instability, arises upon different types of DNA replication perturbations, including those that stall replication fork progression. Inhibitors of the cellular pool of deoxynucleotide triphosphates (dNTPs) slow down DNA synthesis throughout the genome. Following depletion of dNTPs, the highly conserved replication checkpoint kinase pathway, also known as the S-phase checkpoint, preserves the functionality and structure of stalled DNA replication forks and prevents chromosome fragmentation...
February 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28196013/prognostic-implications-of-expression-profiling-for-gemcitabine-related-genes-hent1-dck-rrm1-rrm2-in-patients-with-resectable-pancreatic-adenocarcinoma-receiving-adjuvant-chemotherapy
#2
Marek Sierzega, Radosław Pach, Piotr Kulig, Janusz Legutko, Jan Kulig
OBJECTIVES: The aim of this study was to examine the relevance of expression profiling of 4 genes involved in the action of gemcitabine among patients with pancreatic ductal-cell adenocarcinoma (PDAC). METHODS: A group of 100 patients who underwent pancreatic resections for PDAC and received adjuvant chemotherapy with gemcitabine between 2007 and 2010 was identified. Expression of mRNAs for human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunits (RRM1, RRM2), and deoxycytidine kinase (dCK) was examined by quantitative real-time polymerase chain reaction, normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and dichotomized into groups of low and moderate/high expression levels grouped by tertiles...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28171730/formal-reduction-potentials-of-difluorotyrosine-and-trifluorotyrosine-protein-residues-defining-the-thermodynamics-of-multistep-radical-transfer
#3
Kanchana R Ravichandran, Allan Bin Zong, Alexander T Taguchi, Daniel G Nocera, JoAnne Stubbe, Cecilia Tommos
Redox-active tyrosines (Ys) play essential roles in enzymes involved in primary metabolism including energy transduction and deoxynucleotide production catalyzed by ribonucleotide reductases (RNRs). Thermodynamic characterization of Ys in solution and in proteins remains a challenge due to the high reduction potentials involved and the reactive nature of the radical state. The structurally characterized α3Y model protein has allowed the first determination of formal reduction potentials (E°') for a Y residing within a protein (Berry, B...
February 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28130843/insufficient-levels-of-the-nrdab-encoded-ribonucleotide-reductase-underlie-the-severe-growth-defect-of-the-%C3%AE-hda-e-coli-strain
#4
Vignesh M P Babu, Mark Itsko, Jamie C Baxter, Roel M Schaaper, Mark D Sutton
The ATP-bound form of the Escherichia coli DnaA replication initiator protein remodels the chromosomal origin of replication, oriC, to load the replicative helicase. The primary mechanism for regulating the activity of DnaA involves the Hda and β clamp proteins, which act together to dramatically stimulate the intrinsic DNA-dependent ATPase activity of DnaA via a process termed Regulatory Inactivation of DnaA (RIDA). In addition to hyper-initiation, strains lacking hda function also exhibit cold sensitive growth at 30°C...
January 27, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28115631/ligand-binding-to-2-deoxyguanosine-sensing-riboswitch-in-metabolic-context
#5
Yong-Boum Kim, Anna Wacker, Karl von Laer, Vladimir V Rogov, Beatrix Suess, Harald Schwalbe
The mfl-riboswitch is a transcriptional off-switch, which down-regulates expression of subunit β of ribonucleotide reductase in Mesoplasma florum upon 2'-deoxyguanosine binding. We characterized binding of 2'-deoxyguanosine to the mfl-aptamer domain (WT aptamer) and a sequence-stabilized aptamer (MT aptamer) under in vitro and 'in-cell-like' conditions by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. 'In-cell-like' environment was simulated by Bacillus subtilis cell extract, in which both aptamers remained sufficiently stable to detect the resonances of structural elements and ligand binding in 2D NMR experiments...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28103007/glutamate-350-plays-an-essential-role-in-conformational-gating-of-long-range-radical-transport-in-escherichia-coli-class-ia-ribonucleotide-reductase
#6
Kanchana Ravichandran, Ellen C Minnihan, Qinghui Lin, Kenichi Yokoyama, Alexander T Taguchi, Jimin Shao, Daniel G Nocera, JoAnne Stubbe
Escherichia coli class Ia ribonucleotide reductase (RNR) is composed of two subunits that form an active α2β2 complex. The nucleoside diphosphate substrates (NDP) are reduced in α2, 35 Å from the essential diferric-tyrosyl radical (Y122(•)) cofactor in β2. The Y122(•)-mediated oxidation of C439 in α2 occurs by a pathway (Y122 ⇆ [W48] ⇆ Y356 in β2 to Y731 ⇆ Y730 ⇆ C439 in α2) across the α/β interface. The absence of an α2β2 structure precludes insight into the location of Y356 and Y731 at the subunit interface...
February 2, 2017: Biochemistry
https://www.readbyqxmd.com/read/28096683/clinicopathological-and-immunohistochemical-features-of-lung-invasive-mucinous-adenocarcinoma-based-on-computed-tomography-findings
#7
Katsuhiko Shimizu, Riki Okita, Shinsuke Saisho, Ai Maeda, Yuji Nojima, Masao Nakata
BACKGROUND: We performed an analysis to clarify differences in clinicopathological and molecular features of lung invasive mucinous adenocarcinoma (IMA) based on computed tomography (CT) findings and their impact on prognosis. PATIENTS AND METHODS: On the basis of CT findings, we divided lung IMA into three subtypes: solid, bubbling, and pneumonic. We then investigated differences in clinicopathological characteristics, prognosis, and the expressions of well-identified biomarkers, including cyclooxygenase-2 (Cox-2), excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M1 (RRM1), class III beta-tubulin, thymidylate synthase (TS), secreted protein acidic and rich in cysteine (SPARC), programmed cell death-1 ligand-1 (PD-L1), and epidermal growth factor receptor mutation, among the three subtypes...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28091524/formate-simultaneously-reduces-oxidase-activity-and-enhances-respiration-in-campylobacter-jejuni
#8
Issmat I Kassem, Rosario A Candelero-Rueda, Kawthar A Esseili, Gireesh Rajashekara
The foodborne microaerophilic pathogen, Campylobacter jejuni, possesses a periplasmic formate dehydrogenase and two terminal oxidases, which serve to metabolize formate and facilitate the use of oxygen as a terminal electron acceptor, respectively. Formate, a primary energy source for C. jejuni, inhibits oxidase activity in other bacteria. Here, we hypothesized that formate might affect both energy metabolism and microaerobic survival in C. jejuni. Subsequently, we showed that C. jejuni 81-176 (wildtype) exhibited enhanced chemoattraction to and respiration of formate in comparison to other organic acids...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28075562/evidence-for-a-di-%C3%AE-oxo-diamond-core-in-the-mn-iv-fe-iv-activation-intermediate-of-ribonucleotide-reductase-from-chlamydia-trachomatis
#9
Ryan J Martinie, Elizabeth J Blaesi, Carsten Krebs, J Martin Bollinger, Alexey Silakov, Christopher J Pollock
High-valent iron and manganese complexes effect some of the most challenging biochemical reactions known, including hydrocarbon and water oxidations associated with the global carbon cycle and oxygenic photosynthesis, respectively. Their extreme reactivity presents an impediment to structural characterization, but their biological importance and potential chemical utility have, nevertheless, motivated extensive efforts toward that end. Several such intermediates accumulate during activation of class I ribonucleotide reductase (RNR) β subunits, which self-assemble dimetal cofactors with stable one-electron oxidants that serve to initiate the enzyme's free-radical mechanism...
January 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28074342/the-presence-of-modified-nucleosides-in-extracellular-fluids-leads-to-the-specific-incorporation-of-5-chlorocytidine-into-rna-and-modulates-the-transcription-and-translation
#10
Caroline Noyon, Thierry Roumeguère, Cédric Delporte, Damien Dufour, Melissa Cortese, Jean-Marc Desmet, Christophe Lelubre, Alexandre Rousseau, Philippe Poelvoorde, Jean Nève, Luc Vanhamme, Karim Zouaoui Boudjeltia, Pierre Van Antwerpen
Myeloperoxidase (MPO) is able to promote several kinds of damage and is involved in mechanisms leading to various diseases such as atherosclerosis or cancers. An example of these damages is the chlorination of nucleic acids, which is considered as a specific marker of the MPO activity. Since 5-chlorocytidine has been recently shown in healthy donor plasmas, this study aimed at discovering if these circulating modified nucleosides could be incorporated into RNA and DNA and if their presence impacts the ability of enzymes involved in the incorporation, transcription, and translation processes...
January 10, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28074332/functional-analysis-of-ribonucleotide-reductase-from-cordyceps-militaris-expressed-in-escherichia-coli
#11
Tatsuya Kato, Suparmin Ahmad, Enoch Y Park
Cordyceps militaris produces cordycepin (3'-deoxyadenosine), which has various activities, including anti-oxidant, anti-tumoral, anti-viral, and anti-inflammatory. Ribonucleotide reductase (RNR) seems to be a candidate to produce cordycepin in C. militaris because RNR catalyzes the reduction of nucleotides to 2'-deoxynucleotides, whose structures are similar to that of cordycepin. However, the role of RNR has not been confirmed yet. In this study, complementary DNAs (cDNAs) of C. militaris RNR (CmRNR) large and small subunits (CmR1 and CmR2) were cloned from C...
January 10, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28068088/a-200-mev-uphill-thermodynamic-landscape-for-radical-transport-in-escherichia-coli-ribonucleotide-reductase-determined-using-fluorotyrosine-substituted-enzymes
#12
Kanchana R Ravichandran, Alexander T Taguchi, Yifeng Wei, Cecilia Tommos, Daniel G Nocera, JoAnne Stubbe
Escherichia coli class Ia ribonucleotide reductase (RNR) converts ribonucleotides to deoxynucleotides. A diferric-tyrosyl radical (Y122•) in one subunit (β2) generates a transient thiyl radical in another subunit (α2) via long-range radical transport (RT) through aromatic amino acid residues (Y122 ⇆ [W48] ⇆ Y356 in β2 to Y731 ⇆ Y730 ⇆ C439 in α2). Equilibration of Y356•, Y731•, and Y730• was recently observed using site specifically incorporated unnatural tyrosine analogs; however, equilibration between Y122• and Y356• has not been detected...
October 19, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28066957/overexpression-of-ribonucleotide-reductase-subunit-m1-protein-predicts-shorter-survival-in-metastatic-bladder-cancer-patients-treated-with-gemcitabine-containing-combination-chemotherapy
#13
Nagahide Matsumura, Yasushi Nakamura, Yasuo Kohjimoto, Satoshi Nishizawa, Kazuro Kikkawa, Akinori Iba, Yoshiki Kodama, Isao Hara
OBJECTIVES: To identify biomarkers predicting prognosis in bladder cancer patients undergoing the gemcitabine and cisplatin regimen. METHODS: We studied 52 patients with metastatic bladder cancer treated with the gemcitabine and cisplatin regimen by evaluating the relationship between the expression of two biomarkers, ribonucleotide reductase subunit M1 and excision repair cross complementing 1, by immunohistochemistry and clinical outcomes. RESULTS: The patients with low expression of ribonucleotide reductase subunit M1 showed a higher objective response rate by the gemcitabine and cisplatin regimen than those with high expression of ribonucleotide reductase subunit M1 (80...
January 9, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28061880/phospho-akt-overexpression-is-prognostic-and-can-be-used-to-tailor-the-synergistic-interaction-of-akt-inhibitors-with-gemcitabine-in-pancreatic-cancer
#14
Daniela Massihnia, Amir Avan, Niccola Funel, Mina Maftouh, Anne van Krieken, Carlotta Granchi, Rajiv Raktoe, Ugo Boggi, Babette Aicher, Filippo Minutolo, Antonio Russo, Leticia G Leon, Godefridus J Peters, Elisa Giovannetti
BACKGROUND: There is increasing evidence of a constitutive activation of Akt in pancreatic ductal adenocarcinoma (PDAC), associated with poor prognosis and chemoresistance. Therefore, we evaluated the expression of phospho-Akt in PDAC tissues and cells, and investigated molecular mechanisms influencing the therapeutic potential of Akt inhibition in combination with gemcitabine. METHODS: Phospho-Akt expression was evaluated by immunohistochemistry in tissue microarrays (TMAs) with specimens tissue from radically-resected patients (n = 100)...
January 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27980346/cytotoxic-gallium-complexes-containing-thiosemicarbazones-derived-from-9-anthraldehyde-molecular-docking-with-biomolecules
#15
Floyd A Beckford, Alyssa Brock, Antonio Gonzalez-Sarrías, Navindra P Seeram
We have synthesized a trio of gallium complexes bearing 9-anthraldehyde thiosemicarbazones. The complexes were assessed for their anticancer activity and their biophysical reactivity was also investigated. The three complexes displayed good cytotoxic profiles against two human colon cancer cell lines, HCT-116 and Caco-2. The IC50 ranged from 4.7 - 44.1 μM with the complex having an unsubstituted amino group on the thiosemicarbazone being the most active. This particular complex also showed a high therapeutic index...
October 5, 2016: Journal of Molecular Structure
https://www.readbyqxmd.com/read/27958354/unusual-five-copies-and-dual-forms-of-nrdb-in-candidatus-liberibacter-asiaticus-biological-implications-and-pcr-detection-application
#16
Zheng Zheng, Meirong Xu, Minli Bao, Fengnian Wu, Jianchi Chen, Xiaoling Deng
"Candidatus Liberibacter asiaticus" (CLas), a non-culturable α-proteobacterium, is associated with citrus Huanglongbing (HLB, yellow shoot disease) currently threatening citrus production worldwide. Here, the whole genome sequence of CLas strain A4 from Guangdong of China was analyzed. Five copies of nrdB, encoding β-subunit of ribonucleotide reductase (RNR), a critical enzyme involving bacterial proliferation, were found. Three nrdB copies were in long form (nrdB(L), 1,059 bp) and two were in short form (nrdB(S), 378 bp)...
December 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27941687/low-dose-methylmercury-induced-genes-regulate-mitochondrial-biogenesis-via-mir-25-in-immortalized-human-embryonic-neural-progenitor-cells
#17
Xinjin Wang, Mengling Yan, Lina Zhao, Qing Wu, Chunhua Wu, Xiuli Chang, Zhijun Zhou
Mitochondria are essential organelles and important targets for environmental pollutants. The detection of mitochondrial biogenesis and generation of reactive oxygen species (ROS) and p53 levels following low-dose methylmercury (MeHg) exposure could expand our understanding of underlying mechanisms. Here, the sensitivity of immortalized human neural progenitor cells (ihNPCs) upon exposure to MeHg was investigated. We found that MeHg altered cell viability and the number of 5-ethynyl-2'-deoxyuridine (EdU)-positive cells...
December 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27932760/-satb1-promotes-the-malignant-of-human-non-hodgkin-lymphoma-by-activating-the-ribonucleotide-reductase-%C3%A2-small-subunit-m2
#18
Dayong Yan, Wei Wang
To explore the role of the special AT rich sequence binding protein-1 (SATB1) and ribonucleotide reductase M2 (RRM2) in enhancing malignant progression of non-Hodgkin lymphoma (NHL). 
 Methods: A total of 42 NHL and 42 chronic lymphadenitis patients were recruited. The protein expressions of SATB1 and RRM2 in cervical lymph nodes were determined by Western blot. After overexpression of SATB1, siSATB1 or siRRM2, the mRNA levels of SATB1 and RRM2 in cells were analyzed via RT-PCR, the cell proliferation was evaluated via MTT and EdU assays, while the migration and invasion of cells were assessed by transwell assays...
November 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27924826/iron-chelators-target-both-proliferating-and-quiescent-cancer-cells
#19
Mårten Fryknäs, Xiaonan Zhang, Ulf Bremberg, Wojciech Senkowski, Maria Hägg Olofsson, Peter Brandt, Ingmar Persson, Padraig D'Arcy, Joachim Gullbo, Peter Nygren, Leoni Kunz Schughart, Stig Linder, Rolf Larsson
Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920297/role-of-ribonucleotide-reductase-in-bacillus-subtilis-stress-associated-mutagenesis
#20
Karla Viridiana Castro-Cerritos, Ronald E Yasbin, Eduardo A Robleto, Mario Pedraza-Reyes
: The Gram-positive microorganism Bacillus subtilis relies on a single class Ib ribonucleotide reductase (RNR) to generate 2'-deoxyribonucleotides (dNDPs) for DNA replication and repair. In this work, we investigated the influence of RNR levels on B. subtilis stationary-phase-associated mutagenesis (SPM). Since RNR is essential in this bacterium, we engineered a conditional mutant of strain B. subtilis YB955 (hisC952 metB5 leu427) in which expression of the nrdEF operon was modulated by isopropyl-β-d-thiogalactopyranoside (IPTG)...
February 15, 2017: Journal of Bacteriology
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