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Ribonucleotide reductase

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https://www.readbyqxmd.com/read/29321311/herpes-simplex-virus-1-mutant-with-point-mutations-in-ul39-is-impaired-for-acute-viral-replication-in-mice-establishment-of-latency-and-explant-induced-reactivation
#1
Heba H Mostafa, Thornton W Thompson, Adam J Konen, Steve D Haenchen, Joshua G Hilliard, Stuart J Macdonald, Lynda A Morrison, David J Davido
In the process of generating HSV-1 mutants in the viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a viral mutant, termed KOS-NA, that was severely impaired for acute replication in the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent infection, and reactivated poorly from explanted TG. To identify the secondary mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced the KOS-NA genome and noted that it contained two nonsynonymous mutations in UL39, which encodes the large subunit of ribonucleotide reductase, ICP6...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29305896/superoxide-dismutase-protects-ribonucleotide-reductase-from-inactivation-in-yeast
#2
Andrew B Das, Izabela Sadowska-Bartosz, Andreas Königstorfer, Anthony J Kettle, Christine C Winterbourn
Ribonucleotide reductase (RNR) catalyses the rate limiting step of DNA synthesis utilising a mechanism that requires a tyrosyl radical. We have previously shown that superoxide can quench protein tyrosyl radicals in vitro, either by oxidative addition, or reduction of the radical to tyrosine. Here, we observe that Saccharomyces cerevisiae strains lacking either copper-zinc SOD (SOD1) or manganese SOD (SOD2) had decreased RNR activity compared to SOD competent yeast. When superoxide production was increased by treatment with paraquat, RNR activity was further decreased, with yeast lacking SOD1 being the most sensitive...
January 3, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29298131/a-systematic-review-of-p53-regulation-of-oxidative-stress-in-skeletal-muscle
#3
Kaitlyn Beyfuss, David A Hood
BACKGROUND: p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. METHODS: A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases...
January 3, 2018: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/29286153/chk1-inhibition-sensitizes-pancreatic-cancer-cells-to-gemcitabine-via-promoting-cdk-dependent-dna-damage-and-ribonucleotide-reductase-downregulation
#4
Min Liang, Tiangang Zhao, Linfeng Ma, Yingjie Guo
Inhibition of checkpoint kinase 1 (CHK1) is a promising therapeutic strategy to increase the effectiveness of DNA-damaging drugs in pancreatic cancer. However, owing to the multiple roles of CHK1 in the DNA damage response (DDR) pathway, the molecular mechanism of chemosensitization by CHK1 inhibitors is not definitive. In the present study, we explored the antitumor mechanism of LY2603618, a specific CHK1 inhibitor, alone or in combination with gemcitabine in 5 pancreatic cancer cell lines. LY2603618 treatment of the pancreatic cancer cell lines resulted in growth inhibition, with IC50 values ranging from 0...
December 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29278740/the-a-to-z-of-modulated-cell-patterning-by-mammalian-thioredoxin-reductases
#5
REVIEW
Markus Dagnell, Edward E Schmidt, Elias S J Arnér
Mammalian thioredoxin reductases (TrxRs) are selenocysteine-containing proteins (selenoproteins) that propel a large number of functions through reduction of several substrates including the active site disulfide of thioredoxins (Trxs). Well-known enzymatic systems that in turn are supported by Trxs and TrxRs include deoxyribonucleotide synthesis through ribonucleotide reductase, antioxidant defense through peroxiredoxins and methionine sulfoxide reductases, and redox modulation of a number of transcription factors...
December 23, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29275122/precision-design-of-nanomedicines-to-restore-gemcitabine-chemosensitivity-for-personalized-pancreatic-ductal-adenocarcinoma-treatment
#6
Xiao Zhao, Xiuchao Wang, Wei Sun, Keman Cheng, Hao Qin, Xuexiang Han, Yu Lin, Yongwei Wang, Jiayan Lang, Ruifang Zhao, Xiaowei Zheng, Ying Zhao, Jian Shi, Jihui Hao, Qing Robert Miao, Guangjun Nie, He Ren
Low chemosensitivity considerably restricts the therapeutic efficacy of gemcitabine (GEM) in pancreatic cancer treatment. Using immunohistochemical evaluation, we investigated that decreased expression of human equilibrative nucleoside transporter-1 (hENT1, which is the major GEM transporter across cell membranes) and increased expression of ribonucleotide reductase subunit 2 (RRM2, which decreases the cytotoxicity of GEM) was associated with low GEM chemosensitivity. To solve these problems, we employed a nanomedicine-based formulation of cationic liposomes for co-delivery of GEM along with siRNA targeting RRM2...
December 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/29249313/in-silico-identification-and-high-throughput-screening-of-antigenic-proteins-as-candidates-for-a-mannheimia-haemolytica-vaccine
#7
Cassidy L Klima, Rahat Zaheer, Shaun R Cook, Jay Rasmussen, Trevor W Alexander, Andrew Potter, Steve Hendrick, Tim A McAllister
This study examined the use of comparative genomic analysis for vaccine design against Mannheimia haemolytica, a respiratory pathogen of ruminants. A total of 2,341genes were identified in at least half of the 23 genomes. Of these, a total of 240 were identified to code for N-terminal signal peptides with diverse sub-cellular localizations (78 periplasmic, 52 outer membrane, 15 extracellular, 13 cytoplasmic membrane and 82 unknown) and were examined in an ELISA assay using a coupled-cell free transcription/translation system for protein expressionwith antisera from cattle challenged with serovars 1, 2 or 6 of M...
January 2018: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29237424/p53r2-as-a-novel-prognostic-biomarker-in-nasopharyngeal-carcinoma
#8
Jiewei Chen, Shuman Li, Yongbo Xiao, Xuan Zou, Xinke Zhang, Mingshu Zhu, Muyan Cai, Dan Xie
BACKGROUND: p53R2 is a target of p53 gene, which is essential for DNA repair, mitochondrial DNA synthesis, protection against oxidative stress, chromosomal instability, chronic inflammation and tumorigenesis. This study is aimed to investigate the expression of ribonucleotide reductase (RR) subunit p53R2 in nasopharyngeal carcinoma and its significance in the prognosis. METHODS: The expression levels of p53R2 in 201 patients with NPC were examined by immunohistochemical assay...
December 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29218640/oxoiron-iv-complexes-as-synthons-for-the-assembly-of-heterobimetallic-centers-such-as-the-fe-mn-active-site-of-class-ic-ribonucleotide-reductases
#9
Ang Zhou, Patrick M Crossland, Apparao Draksharapu, Andrew J Jasniewski, Scott T Kleespies, Lawrence Que
Nonheme oxoiron(IV) complexes can serve as synthons for generating heterobimetallic oxo-bridged dimetal complexes by reaction with divalent metal complexes. The formation of FeIII-O-CrIII and FeIII-O-MnIII complexes is described herein. The latter complexes may serve as models for the FeIII-X-MnIII active sites of an emerging class of Fe/Mn enzymes represented by the Class 1c ribonucleotide reductase from Chlamydia trachomatis and the R2-like ligand-binding oxidase (R2lox) found in Mycobacterium tuberculosis...
December 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29214667/effect-of-ribonucleotide-reductase-m1-expression-on-overall-survival-in-patients-with-pancreatic-cancer-receiving-gemcitabine-chemotherapy-a-literature-based-meta-analysis
#10
REVIEW
Q L Han, Y H Zhou, Y Lyu, H Yan, G H Dai
WHAT IS KNOWN AND OBJECTIVE: The prognostic value of ribonucleotide reductase M1 (RRM1) in patients with pancreatic cancer receiving gemcitabine chemotherapy has been evaluated in several studies. However, the conclusions remain controversial. METHODS: By searching the PubMed and Embase databases, we conducted a meta-analysis to evaluate the prognostic significance of RRM1 expression in patients with pancreatic cancer receiving gemcitabine chemotherapy. Studies were pooled, and the hazard ratio (HR) and its corresponding 95% confidence interval (CI) were calculated...
December 6, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29165865/mimicking-class-ib-mn2-ribonucleotide-reductase-a-mnii2-complex-and-its-reaction-with-superoxide
#11
Adriana Magherusan, Ang Zhou, Erik Farquhar, Max Garcia Melchor, Brendan Twamley, Lawrence Que, Aidan Richard McDonald
Class Ib RNRs require superoxide anion (O2*-), rather than dioxygen (O2), to access a high-valent Mn2 oxidant. Complex 1 ([Mn2(O2CCH3)(N-Et-HPTB)](ClO4)2, N-Et-HPTB = N,N,N',N'-tetrakis(2-(1-ethylbenzimidazolyl))-2-hydroxy-1,3-diaminopropane) was synthesised in high yield (90%). 1 was reacted with O2*- at -40 °C resulting in the formation of a metastable species (2). 2 displayed electronic absorption features (λmax = 460, 610 nm) typical of a Mn-peroxide species, and a 29 line EPR signal typical of a MnIIMnIII entity...
November 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29155068/a-noncanonical-poly-a-rna-polymerase-gene-affects-morphology-in-phoma-medicaginis
#12
Kihyuck Choi, Stephen M Marek
Phoma medicaginis (syn. Ascochyta medicaginicola Qchen &L. Cai) causes spring black stem and leaf spot, an important disease of alfalfa and annual medics. P. medicaginis forms uninucleate conidia in melanized pycnidia and is genetically tractable using Agrobacterium mediated transformation (ATMT), resulting in random integration of T-DNA that occasionally generates pycnidial mutants. The T-DNA tagged mutant, P265 displayed smaller pycnidia and more aerial hyphae than the wild type. A single T-DNA disrupted a putative noncanonical poly(A) RNA polymerase gene, Pmncpap1, which in yeast interacts with ribonucleotide reductase (RNR)...
November 15, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29152060/inhibition-of-chk1-sensitizes-ewing-sarcoma-cells-to-the-ribonucleotide-reductase-inhibitor-gemcitabine
#13
Kelli L Goss, Stacia L Koppenhafer, Kathryn M Harmoney, William W Terry, David J Gordon
Ewing sarcoma is a bone and soft tissue sarcoma that occurs in children and young adults. The EWS-FLI1 gene fusion is the driver mutation in most Ewing sarcoma tumors and functions, in part, as an aberrant transcription factor. We recently identified that Ewing sarcoma cells are sensitive to inhibition of ribonucleotide reductase (RNR), which catalyzes the formation of deoxyribonucleotides from ribonucleotides. In this report, we show that Ewing sarcoma cells are sensitive to treatment with clofarabine, which is a nucleoside analogue and allosteric inhibitor of RNR...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138305/manipulating-the-bacterial-cell-cycle-and-cell-size-by-titrating-the-expression-of-ribonucleotide-reductase
#14
Manlu Zhu, Xiongfeng Dai, Weilun Guo, Zengxiang Ge, Mingxuan Yang, Haikuan Wang, Yi-Ping Wang
Understanding how bacteria coordinate growth with cell cycle events to maintain cell size homeostasis remains a grand challenge in biology. The period of chromosome replication (C period) is a key stage in the bacterial cell cycle. However, the mechanism of in vivo regulation of the C period remains unclear. In this study, we found that titration of the expression of ribonucleotide reductase (RNR), which changes the intracellular deoxynucleoside triphosphate (dNTP) pools, enables significant perturbations of the C period, leading to a substantial change in cell size and DNA content...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29123070/redox-sensitive-alteration-of-replisome-architecture-safeguards-genome-integrity
#15
Kumar Somyajit, Rajat Gupta, Hana Sedlackova, Kai John Neelsen, Fena Ochs, Maj-Britt Rask, Chunaram Choudhary, Jiri Lukas
DNA replication requires coordination between replication fork progression and deoxynucleotide triphosphate (dNTP)-generating metabolic pathways. We find that perturbation of ribonucleotide reductase (RNR) in humans elevates reactive oxygen species (ROS) that are detected by peroxiredoxin 2 (PRDX2). In the oligomeric state, PRDX2 forms a replisome-associated ROS sensor, which binds the fork accelerator TIMELESS when exposed to low levels of ROS. Elevated ROS levels generated by RNR attenuation disrupt oligomerized PRDX2 to smaller subunits, whose dissociation from chromatin enforces the displacement of TIMELESS from the replisome...
November 10, 2017: Science
https://www.readbyqxmd.com/read/29119271/rnr1-s-role-in-telomere-elongation-cannot-be-replaced-by-rnr3-a-role-beyond-dntps
#16
REVIEW
André Maicher, Martin Kupiec
Telomeres, the nucleoprotein complexes at the end of eukaryotic chromosomes, protect them from degradation and ensure the replicative capacity of cells. In most human tumors and in budding yeast, telomere length is maintained by the activity of telomerase, an enzyme that adds dNTPs according to an internal RNA template. The dNTPs are generated with the help of the ribonucleotide reductase (RNR) complex. We have recently generated strains lacking the large subunit of RNR, Rnr1, which were kept viable by the expression of RNR complexes containing the Rnr1 homolog, Rnr3...
November 8, 2017: Current Genetics
https://www.readbyqxmd.com/read/29113399/dck-expression-a-potential-predictive-biomarker-in-the-adjuvant-gemcitabine-chemotherapy-for-biliary-tract-cancer-after-surgical-resection-results-from-a-phase-ii-study
#17
Sang Myung Woo, Kyong-Ah Yoon, Eun Kyung Hong, Weon Seo Park, Sung-Sik Han, Sang-Jae Park, Jungnam Joo, Eun Young Park, Ju Hee Lee, Yun-Hee Kim, Tae Hyun Kim, Woo Jin Lee
The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. This clinical phase II trial was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patients were started on intravenous infusions of gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of every 28-day cycle. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29111571/n-4-aryl-substituted-thiosemicarbazones-derived-from-1-indanones-as-potential-anti-tumor-agents-for-breast-cancer-treatment
#18
A Sólimo, M C Soraires Santacruz, A I Loaiza Perez, E Bal de Kier Joffé, L M Finkielsztein, M A Callero
Breast cancer is the first cause of cancer death in women. Many patients are resistant to current therapies, and even those were sensitive at first may eventually become resistant later. Thiosemicarbazones (TSCs) are synthetic compounds that exhibit several pharmacological activities. In this study, we investigated the potential anti-tumor activity of a set of N(4) -arylsubstituted TSCs (N(4) -TSCs) on human breast cancer cell lines. Studies on the effect of N(4) -TSCs (T1, T2 and T3) were carried on MCF-7, MDA-MB 231 and BT 474 cell lines which differ in their expression of ER, PR and Her2/neu...
November 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29100320/suppression-of-pancreatic-adenocarcinoma-upregulated-factor-pauf-increases-the-sensitivity-of-pancreatic-cancer-to-gemcitabine-and-5fu-and-inhibits-the-formation-of-pancreatic-cancer-stem-like-cells
#19
Jae Hee Cho, Sun A Kim, Soo Been Park, Hee Man Kim, Si Young Song
Pancreatic cancer stem cells (CSCs) play a crucial role in tumorigenesis and chemoresistance of pancreatic ductal adenocarcinoma. Pancreatic adenocarcinoma up-regulated factor (PAUF), a novel secretory protein, has been shown to contribute to cancer progression and metastasis. Because the clinical relationship between PAUF and pancreatic CSCs is largely unknown, we investigated the associations between the functional role of PAUF and pancreatic CSCs. Pancreatic cancer sphere cultured from the CFPAC-1 cells showed elevated expression of PAUF and pluripotent stemness genes (Oct4, Nanog, Stat3, and Sox2), and the mRNA of PAUF were increased in CD44(+)CD24(+)ESA(+) pancreatic CSCs...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29099956/recycling-drug-screen-repurposes-hydroxyurea-as-a-sensitizer-of-glioblastomas-to-temozolomide-targeting-de-novo-dna-synthesis-irrespective-of-molecular-subtype
#20
Jian Teng, Seyedali Hejazi, Lotte Hiddingh, Litia Carvalho, Mark de Gooijer, Hiroaki Wakimoto, Marco Barazas, Marie Tannous, Andrew S Chi, David P Noske, Pieter Wesseling, Thomas Wurdinger, Tracy T Batchelor, Bakhos A Tannous
Background: Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor. Standard-of-care treatment involves maximal surgical resection of the tumor followed by radiation and chemotherapy (temozolomide; TMZ). The five-year survival rate of patients with GBM is <10%, a colossal failure that has been partially attributed to intrinsic and/or acquired resistance to TMZ through MGMT (O6-methylguanine DNA methyltransferase) promoter methylation status in the tumor...
November 1, 2017: Neuro-oncology
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