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Ribonucleotide reductase

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https://www.readbyqxmd.com/read/28640807/lack-of-a-peroxiredoxin-suppresses-the-lethality-of-cells-devoid-of-electron-donors-by-channelling-electrons-to-oxidized-ribonucleotide-reductase
#1
Susanna Boronat, Alba Domènech, Mercè Carmona, Sarela García-Santamarina, M Carmen Bañó, José Ayté, Elena Hidalgo
The thioredoxin and glutaredoxin pathways are responsible of recycling several enzymes which undergo intramolecular disulfide bond formation as part of their catalytic cycles such as the peroxide scavengers peroxiredoxins or the enzyme ribonucleotide reductase (RNR). RNR, the rate-limiting enzyme of deoxyribonucleotide synthesis, is an essential enzyme relying on these electron flow cascades for recycling. RNR is tightly regulated in a cell cycle-dependent manner at different levels, but little is known about the participation of electron donors in such regulation...
June 22, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28640584/spectroscopic-evidence-for-a-h-bond-network-at-y356-located-at-the-subunit-interface-of-active-e-coli-ribonucleotide-reductase
#2
Thomas U Nick, Kanchana R Ravichandran, JoAnne Stubbe, Müge Kasanmascheff, Marina Bennati
The reaction catalyzed by E. coli ribonucleotide reductase (RNR) composed of α and β subunits that form an active α2β2 complex is a paradigm for proton-coupled electron transfer (PCET) processes in biological transformations. β2 contains the diferric tyrosyl radical (Y122•) cofactor that initiates a radical transfer (RT) over 35 Å via a specific pathway of amino acids (Y122• ↔ [W48] ↔ Y356 in β2 to Y731 ↔Y730↔ C439 in α2). Experimental evidence exists for co-linear and orthogonal PCET in α2 and β2 respectively...
June 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28640074/bioinformatics-analysis-of-key-genes-and-pathways-for-hepatocellular-carcinoma-transformed-from-cirrhosis
#3
Bosheng He, Jianbing Yin, Shenchu Gong, Jinhua Gu, Jing Xiao, Weixiang Shi, Wenbin Ding, Ying He
OBJECTIVE: We aimed to identify some pivotal genes and pathways for hepatocellular carcinoma (HCC) transformation from cirrhosis and explore potential targets for treatment of the disease. METHODS: The GSE17548 microarray data were downloaded from Gene Expression Omnibus database, and 37 samples (20 cirrhosis and 17 HCC samples) were used for analysis. The differentially expressed genes (DEGs) in HCC tissues were compared with those in cirrhosis tissues and analyzed using the limma package...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28624910/clinical-pharmacology-and-clinical-trials-of-ribonucleotide-reductase-inhibitors-is-it-a-viable-cancer-therapy
#4
REVIEW
Mukundan Baskar Mannargudi, Subrata Deb
PURPOSE: Ribonucleotide reductase (RR) enzymes (RR1 and RR2) play an important role in the reduction of ribonucleotides to deoxyribonucleotides which is involved in DNA replication and repair. Augmented RR activity has been ascribed to uncontrolled cell growth and tumorigenic transformation. METHODS: This review mainly focuses on several biological and chemical RR inhibitors (e.g., siRNA, GTI-2040, GTI-2501, triapine, gemcitabine, and clofarabine) that have been evaluated in clinical trials with promising anticancer activity from 1960's till 2016...
June 17, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28624879/lc-ms-ms-proteomic-analysis-of-starved-bacillus-subtilis-cells-overexpressing-ribonucleotide-reductase-nrdef-implications-in-stress-associated-mutagenesis
#5
Karla Viridiana Castro-Cerritos, Adolfo Lopez-Torres, Armando Obregón-Herrera, Katarzyna Wrobel, Kazimierz Wrobel, Mario Pedraza-Reyes
The non-appropriate conditions faced by nutritionally stressed bacteria propitiate error-prone repair events underlying stationary-phase- or stress-associated mutagenesis (SPM). The genetic and molecular mechanisms involved in SPM have been deeply studied but the biochemical aspects of this process have so far been less explored. Previous evidence showed that under conditions of nutritional stress, non-dividing cells of strain B. subtilis YB955 overexpressing ribonucleotide reductase (RNR) exhibited a strong propensity to generate true reversions in the hisC952 (amber), metB5 (ochre) and leuC425 (missense) mutant alleles...
June 17, 2017: Current Genetics
https://www.readbyqxmd.com/read/28606995/synergistic-antibacterial-effect-of-silver-and-ebselen-against-multidrug-resistant-gram-negative-bacterial-infections
#6
Lili Zou, Jun Lu, Jun Wang, Xiaoyuan Ren, Lanlan Zhang, Yu Gao, Martin E Rottenberg, Arne Holmgren
Multidrug-resistant (MDR) Gram-negative bacteria account for a majority of fatal infections, and development of new antibiotic principles and drugs is therefore of outstanding importance. Here, we report that five most clinically difficult-to-treat MDR Gram-negative bacteria are highly sensitive to a synergistic combination of silver and ebselen. In contrast, silver has no synergistic toxicity with ebselen on mammalian cells. The silver and ebselen combination causes a rapid depletion of glutathione and inhibition of the thioredoxin system in bacteria...
June 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28604743/shortage-of-dntps-underlies-altered-replication-dynamics-and-dna-breakage-in-the-absence-of-the-apc-c-cofactor-cdh1
#7
J Garzón, R Rodríguez, Z Kong, A Chabes, S Rodríguez-Acebes, J Méndez, S Moreno, I García-Higuera
The APC/C-Cdh1 ubiquitin-ligase complex targets cell cycle regulators for proteosomal degradation and helps prevent tumor development and accumulation of chromosomal aberrations. Replication stress has been proposed to be the main driver of genomic instability in the absence of Cdh1, but the real contribution of APC/C-Cdh1 to efficient replication, especially in normal cells, remains unclear. Here we show that, in primary MEFs, acute depletion or permanent ablation of Cdh1 slowed down replication fork movement and increased origin activity...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28578018/rice-gene-sdl-rnrs1-encoding-the-small-subunit-of-ribonucleotide-reductase-is-required-for-chlorophyll-synthesis-and-plant-growth-development
#8
Ran Qin, Dongdong Zeng, Rong Liang, Chengcong Yang, Delara Akhter, Alamin Md, Xiaoli Jin, Chunhai Shi
A new mutant named sdl (stripe and drooping leaf) was characterized from indica cultivar Zhenong 34 by ethylmethane sulfonate (EMS) mutagenesis. The mutant sdl exhibited development defects including stripe and drooping leaf, dwarfism and deformed floral organs. The gene SDL was found allelic to RNRS1 by map-based cloning, which was homologous to Arabidopsis TSO2 encoding the small subunit of ribonucleotide reductase. The gDNA sequencing results of sdl in mutant consistently showed that there was a repetitive sequence insertion of 138-bp at the 475th bp in the exon...
May 31, 2017: Gene
https://www.readbyqxmd.com/read/28570668/cooperative-inhibition-of-rip1-mediated-nf-%C3%AE%C2%BAb-signaling-by-cytomegalovirus-encoded-deubiquitinase-and-inactive-homolog-of-cellular-ribonucleotide-reductase-large-subunit
#9
Ki Mun Kwon, Se Eun Oh, Young Eui Kim, Tae-Hee Han, Jin-Hyun Ahn
Several viruses have been found to encode a deubiquitinating protease (DUB). These viral DUBs are proposed to play a role in regulating innate immune or inflammatory signaling. In human cytomegalovirus (HCMV), the largest tegument protein encoded by UL48 contains DUB activity, but its cellular targets are not known. Here, we show that UL48 and UL45, an HCMV-encoded inactive homolog of cellular ribonucleotide reductase (RNR) large subunit (R1), target receptor-interacting protein kinase 1 (RIP1) to inhibit NF-κB signaling...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28553667/translation-of-cardiac-myosin-activation-with-2-deoxy-atp-to-treat-heart-failure-via-an-experimental-ribonucleotide-reductase-based-gene-therapy
#10
Kassandra S Thomson, Guy L Odom, Charles E Murry, Gregory G Mahairas, Farid Moussavi-Harami, Sam L Teichman, Xiaolan Chen, Stephen D Hauschka, Jeffrey S Chamberlain, Michael Regnier
Despite recent advances, chronic heart failure remains a significant and growing unmet medical need, reaching epidemic proportions carrying substantial morbidity, mortality, and costs. A safe and convenient therapeutic agent that produces sustained inotropic effects could ameliorate symptoms, and improve functional capacity and quality of life. We discovered small amounts of 2-deoxy-ATP (dATP) activate cardiac myosin leading to enhanced contractility in normal and failing heart muscle. Cardiac myosin activation triggers faster myosin crossbridge cycling with greater force generation during each contraction...
December 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28521448/clinical-implications-of-ribonucleotide-reductase-subunit-m1-in-patients-with-pancreatic-cancer-who-undergo-curative-resection-followed-by-adjuvant-chemotherapy-with-gemcitabine
#11
Toru Aoyama, Yohei Miyagi, Masaaki Murakawa, Koichiro Yamaoku, Yosuke Atsumi, Manabu Shiozawa, Makoto Ueno, Manabu Morimoto, Takashi Oshima, Norio Yukawa, Takaki Yoshikawa, Yasushi Rino, Munetaka Masuda, Soichiro Morinaga
To the best of our knowledge, the clinical implications of using ribonucleoside reductase subunit M1 (RRM1) in patients who undergo curative resection and adjuvant chemotherapy have not been established. In the present study, the clinical data from 101 consecutive patients who underwent macroscopically curative resection, and who received adjuvant gemcitabine chemotherapy for pancreatic cancer at the Kanagawa Cancer Centre (Yokohama, Kanagawa, Japan) between April 2005 and December 2014 were retrospectively analyzed...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515324/the-diferric-tyrosyl-radical-cluster-of-ribonucleotide-reductase-and-cytosolic-iron-sulfur-clusters-have-distinct-and-similar-biogenesis-requirements
#12
Haoran Li, Martin Stümpfig, Caiguo Zhang, Xiuxiang An, JoAnne Stubbe, Roland Lill, Mingxia Huang
How each metalloprotein assembles the correct metal at the proper binding site presents challenges to the cell. The di-iron enzyme ribonucleotide reductase (RNR) uses a diferric-tyrosyl radical (Fe(III)2-Y·) cofactor to initiate nucleotide reduction. Assembly of this cofactor requires O2, Fe(II), and a reducing equivalent. Recent studies show that RNR cofactor biosynthesis shares the same source of iron, in the form of [2Fe-2S]-GSH2 from the monothiol glutaredoxin Grx3/4, and the same electron source, in the form of the Dre2-Tah18 electron transfer chain, with the cytosolic iron-sulfur protein assembly (CIA) machinery required for maturation of [4Fe-4S] clusters in cytosolic and nuclear proteins...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28512059/genome-scale-metabolic-network-of-cordyceps-militaris-useful-for-comparative-analysis-of-entomopathogenic-fungi
#13
Wanwipa Vongsangnak, Nachon Raethong, Warasinee Mujchariyakul, Nam Ninh Nguyen, Hon Wai Leong, Kobkul Laoteng
The first genome-scale metabolic network of Cordyceps militaris (iWV1170) was constructed representing its whole metabolisms, which consisted of 894 metabolites and 1,267 metabolic reactions across five compartments, including the plasma membrane, cytoplasm, mitochondria, peroxisome and extracellular space. The iWV1170 could be exploited to explain its phenotypes of growth ability, cordycepin and other metabolites production on various substrates. A high number of genes encoding extracellular enzymes for degradation of complex carbohydrates, lipids and proteins were existed in C...
May 13, 2017: Gene
https://www.readbyqxmd.com/read/28507282/p53-suppresses-ribonucleotide-reductase-via-inhibiting-mtorc1
#14
Zhengfu He, Xing Hu, Weijin Liu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28502800/microrna-211-regulates-oxidative-phosphorylation-and-energy-metabolism-in-human-vitiligo
#15
Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J Perera
Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing (RNA-seq), targeted metabolomics, and shotgun lipidomics...
May 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28495531/the-forkhead-like-transcription-factor-fhl1p-maintains-yeast-replicative-lifespan-by-regulating-ribonucleotide-reductase-1-rnr1-gene-transcription
#16
Akiko Tai, Yuka Kamei, Yukio Mukai
In eukaryotes, numerous genetic factors contribute to the lifespan including metabolic enzymes, signal transducers, and transcription factors. As previously reported, the forkhead-like transcription factor (FHL1) gene was required for yeast replicative lifespan and cell proliferation. To determine how Fhl1p regulates the lifespan, we performed a DNA microarray analysis of a heterozygous diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which were then screened for lifespan-regulating activity...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28487404/long-range-proton-coupled-electron-transfer-in-the-escherichia-coli-class-ia-ribonucleotide-reductase
#17
REVIEW
Steven Y Reece, Mohammad R Seyedsayamdost
Escherichia coli class Ia ribonucleotide reductase (RNR) catalyzes the conversion of nucleotides to 2'-deoxynucleotides using a radical mechanism. Each turnover requires radical transfer from an assembled diferric tyrosyl radical (Y•) cofactor to the enzyme active site over 35 Å away. This unprecedented reaction occurs via an amino acid radical hopping pathway spanning two protein subunits. To study the mechanism of radical transport in RNR, a suite of biochemical approaches have been developed, such as site-directed incorporation of unnatural amino acids with altered electronic properties and photochemical generation of radical intermediates...
May 9, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28472930/three-novel-pseudomonas-phages-isolated-from-composting-provide-insights-into-the-evolution-and-diversity-of-tailed-phages
#18
Deyvid Amgarten, Layla Farage Martins, Karen Cristina Lombardi, Luciana Principal Antunes, Ana Paula Silva de Souza, Gianlucca Gonçalves Nicastro, Elliott Watanabe Kitajima, Ronaldo Bento Quaggio, Chris Upton, João Carlos Setubal, Aline Maria da Silva
BACKGROUND: Among viruses, bacteriophages are a group of special interest due to their capacity of infecting bacteria that are important for biotechnology and human health. Composting is a microbial-driven process in which complex organic matter is converted into humus-like substances. In thermophilic composting, the degradation activity is carried out primarily by bacteria and little is known about the presence and role of bacteriophages in this process. RESULTS: Using Pseudomonas aeruginosa as host, we isolated three new phages from a composting operation at the Sao Paulo Zoo Park (Brazil)...
May 4, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28469953/microrna-1468-5p-inhibits-glioma-cell-proliferation-and-induces-cell-cycle-arrest-by-targeting-rrm1
#19
Kuan Jiang, Tongle Zhi, Wenhui Xu, Xiupeng Xu, Weining Wu, Tianfu Yu, Er Nie, Xu Zhou, Zhongyuan Bao, Xin Jin, Junxia Zhang, Yingyi Wang, Ning Liu
MicroRNAs are associated with different types of cancers. In this study, we found that miR-1468-5p could inhibit growth and cell cycle progression in glioma by targeting ribonucleotide reductase large subunit M1 (RRM1). First, we analyzed miR-1468-5p expression in different glioma grades and the prognostic significance of its expression in glioblastoma multiform patients from the Chinese Glioma Genome Atlas. Then, we expressed miR-1468-5p in U87 and U251 cells and assessed the effects on proliferation and cell cycle progression using cell counting kit-8, colony formation, EdU and flow cytometry assays...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28468907/gsk-3%C3%A3-homolog-rim11-and-the-histone-deacetylase-complex-ume6-sin3-rpd3-are-involved-in-replication-stress-response-caused-by-defects-in-dna2
#20
Annie Albert Demin, Miju Lee, Chul-Hwan Lee, Yeon-Soo Seo
Lagging strand synthesis is mechanistically far more complicated than leading strand synthesis, since it involves multi-step processes and requires considerably more enzymes and protein factors. Due to this complexity, multiple fail-safe factors are required to ensure successful replication of the lagging strand DNA. We attempted to identify novel factors that are required in the absence of the helicase activity of Dna2, an essential enzyme in Okazaki fragment maturation. In this paper, we identified Rim11, a GSK-3ß kinase homolog, as a multicopy suppressor of dna2 helicase-dead mutant (dna2-K1080E)...
May 3, 2017: Genetics
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