keyword
MENU ▼
Read by QxMD icon Read
search

Ribonucleotide reductase

keyword
https://www.readbyqxmd.com/read/27924826/iron-chelators-target-both-proliferating-and-quiescent-cancer-cells
#1
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-on-bacillus-subtilis-stress-associated-mutagenesis
#2
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 in the strain B. subtilis YB955 (hisC952, metB5, leu427) in which expression of the nrdEF operon was modulated by isopropyl-β-D-thiogalactopyranoside (IPTG)...
December 5, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27919952/molecular-factors-associated-with-pemetrexed-sensitivity-according-to-histological-type-in-non-small-cell-lung-cancer
#3
Tsukihisa Yoshida, Tatsuro Okamoto, Tokujiro Yano, Kazuki Takada, Mikihiro Kohno, Kenichi Suda, Mitsuhiro Takenoyama, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: This study was designed to investigate potential molecules that predict chemosensitivity to pemetrexed (Alimta®) in surgically resected non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Chemosensitivity to ALM and other drugs was assessed by succinate dehydrogenase inhibition (SDI) test in 69 NSCLC samples (55 adenocarcinomas, and 14 squamous cell carcinomas). The mRNA expression levels of Alimta®-target enzymes [thymidylate synthase (TYMS); dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT)], Alimta®-metabolizing enzymes [γ-glutamyl hydrase (GGH) and folylpolyglutamate synthase] and an Alimta® transporter [reduce folate carrier (RFC)] were measured and examined for potential correlations to chemosensitivity...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27908619/correlation-of-dna-repair-gene-polymorphisms-with-clinical-outcome-in-patients-with-locally-advanced-non-small-cell-lung-cancer-receiving-induction-chemotherapy-followed-by-surgery
#4
Mariacarmela Santarpia, Jose Luis Ramirez, Itziar de Aguirre, Pilar Garrido, Maria Pérez Cano, Cristina Queralt, Jose Luis Gonzalez-Larriba, Amelia Insa, Mariano Provencio, Dolores Isla, Carlos Camps, Remei Blanco, Teresa Moran, Rafael Rosell
OBJECTIVE: The aim of this study was to evaluate whether xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) polymorphisms influenced clinical outcome in patients with stage IIIA-B non-small-cell lung cancer (NSCLC) treated with neoadjuvant gemcitabine/cisplatin/docetaxel followed by surgery. MATERIALS AND METHODS: A total of 109 patients with stage IIIA and IIIB NSCLC were prospectively genotyped to examine a potential association between XPD 312 (aspartic acid [Asp]/asparagine [Asn]), XPD 751 (lysine [Lys]/glutamine [Gln]), and RRM1 (-37 C/A) polymorphisms with response and survival...
November 9, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27906631/mitochondrial-purine-and-pyrimidine-metabolism-and-beyond
#5
Liya Wang
Carefully balanced deoxynucleoside triphosphate (dNTP) pools are essential for both nuclear and mitochondrial genome replication and repair. Two synthetic pathways operate in cells to produce dNTPs, e.g., the de novo and the salvage pathways. The key regulatory enzymes for de novo synthesis are ribonucleotide reductase (RNR) and thymidylate synthase (TS), and this process is considered to be cytosolic. The salvage pathway operates both in the cytosol (TK1 and dCK) and the mitochondria (TK2 and dGK). Mitochondrial dNTP pools are separated from the cytosolic ones owing to the double membrane structure of the mitochondria, and are formed by the salvage enzymes TK2 and dGK together with NMPKs and NDPK in postmitotic tissues, while in proliferating cells the mitochondrial dNTPs are mainly imported from the cytosol produced by the cytosolic pathways...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27878356/phase-i-trial-of-daily-triapine-in-combination-with-cisplatin-chemotherapy-for-advanced-stage-malignancies
#6
Charles A Kunos, Edward Chu, Jan H Beumer, Mario Sznol, S Percy Ivy
PURPOSE: Advanced-stage malignancies have increased deoxyribonucleotide demands in DNA replication and repair, making deoxyribonucleotide supply a potential exploitable target for therapy based on ribonucleotide reductase (RNR) inhibition. METHODS: A dose-finding phase I trial was conducted of intravenous (i.v.) triapine, a small-molecule RNR inhibitor, and cisplatin chemotherapy in patients with advanced-stage solid tumor malignancies. Patients received dose-finding levels of i...
November 22, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27869662/the-cell-killing-mechanisms-of-hydroxyurea
#7
REVIEW
Amanpreet Singh, Yong-Jie Xu
Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has a long history of scientific interest and clinical use for the treatment of neoplastic and non-neoplastic diseases. It is currently the staple drug for the management of sickle cell anemia and chronic myeloproliferative disorders. Due to its reversible inhibitory effect on DNA replication in various organisms, hydroxyurea is also commonly used in laboratories for cell cycle synchronization or generating replication stress. However, incubation with high concentrations or prolonged treatment with low doses of hydroxyurea can result in cell death and the DNA damage generated at arrested replication forks is generally believed to be the direct cause...
November 17, 2016: Genes
https://www.readbyqxmd.com/read/27866984/p53r2-regulates-thioredoxin-reductase-activity-through-interaction-with-trxr2
#8
Seon-Joo Park, Hong Beum Kim, Chunmei Piao, Mi Yeong Kang, Sang-Gon Park, Seok Won Kim, Jung-Hee Lee
Ribonucleotide reductase small subunit p53R2 is a member of the ribonucleotide reductase family that supplies dNTPs for nuclear and mitochondrial DNA replication and repair. Here, we have identified a mitochondrial thioredoxin reductase 2 (TrxR2) as a novel p53R2-binding protein. We demonstrated a direct interaction between the two, and observed that p53R2 stimulated the enzymatic activity of TrxR in vitro. Moreover, TrxR2 activity was significantly lower in p53R2 knockdown cells, and increased when p53R2 was overexpressed, effects that were independent of p53...
November 17, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27856328/the-therapeutic-potential-of-iron-targeting-gallium-compounds-in-human-disease-from-basic-research-to-clinical-application
#9
REVIEW
Christopher R Chitambar
Gallium, group IIIa metal, shares certain chemical characteristics with iron which enable it to function as an iron mimetic that can disrupt iron-dependent tumor cell growth. Gallium may also display antimicrobial activity by disrupting iron homeostasis in certain bacteria and fungi. Gallium's action on iron homeostasis leads to inhibition of ribonucleotide reductase, mitochondrial function, and changes in proteins of iron transport and storage. In addition, gallium induces an increase in mitochondrial reactive oxygen species in cells which triggers downstream upregulation of metallothionein and hemoxygenase-1...
November 14, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27845436/profiling-ribonucleotide-and-deoxyribonucleotide-pools-perturbed-by-gemcitabine-in-human-non-small-cell-lung-cancer-cells
#10
Jian-Ru Guo, Qian-Qian Chen, Christopher Wai Kei Lam, Cai-Yun Wang, Vincent Kam Wai Wong, Zee-Fen Chang, Wei Zhang
In this study, we investigated the dosage effect of gemcitabine, an inhibitor of ribonucleotide reductase (RR), on cellular levels of ribonucleotides and deoxyribonucleotides using high performance liquid chromatography-electrospray ionization tandem mass spectrometric method. As anticipated, after 4-h incubation of non-small cell lung cancer (A549) cells with gemcitabine at 0.5 and 2 μM, there were consistent reductions in levels of deoxyribonucleoside diphosphates (dNDP) and their corresponding deoxyribonucleoside triphosphates (dNTP)...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27845331/brca1-regulated-rrm2-expression-protects-glioblastoma-cells-from-endogenous-replication-stress-and-promotes-tumorigenicity
#11
Rikke D Rasmussen, Madhavsai K Gajjar, Lucie Tuckova, Kamilla E Jensen, Apolinar Maya-Mendoza, Camilla B Holst, Kjeld Møllgaard, Jane S Rasmussen, Jannick Brennum, Jiri Bartek, Martin Syrucek, Eva Sedlakova, Klaus K Andersen, Marie H Frederiksen, Jiri Bartek, Petra Hamerlik
Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis...
November 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/27812878/detection-of-nucleotide-disbalance-in-cells-undergoing-oncogene-induced-senescence
#12
Mikhail A Nikiforov, Donna S Shewach
DNA damage response has been characterized as an important mediator of senescence phenotypes induced by activated oncogenes in normal human cells. Depletion of intracellular deoxyribonucleotide pools has been recently recognized as one of the major causes for DNA damage in these cells. Cells undergoing oncogene-induced senescence display decreased expression of several rate-limiting enzymes involved in the biosynthesis of deoxyribonucleotides, including thymidylate synthase (TS) and ribonucleotide reductase (RR)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27806303/hydroxyurea-mediated-cytotoxicity-without-inhibition-of-ribonucleotide-reductase
#13
Li Phing Liew, Zun Yi Lim, Matan Cohen, Ziqing Kong, Lisette Marjavaara, Andrei Chabes, Stephen D Bell
In many organisms, hydroxyurea (HU) inhibits class I ribonucleotide reductase, leading to lowered cellular pools of deoxyribonucleoside triphosphates. The reduced levels for DNA precursors is believed to cause replication fork stalling. Upon treatment of the hyperthermophilic archaeon Sulfolobus solfataricus with HU, we observe dose-dependent cell cycle arrest, accumulation of DNA double-strand breaks, stalled replication forks, and elevated levels of recombination structures. However, Sulfolobus has a HU-insensitive class II ribonucleotide reductase, and we reveal that HU treatment does not significantly impact cellular DNA precursor pools...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27801665/creb1-directly-activates-the-transcription-of-ribonucleotide-reductase-small-subunit-m2-and-promotes-the-aggressiveness-of-human-colorectal-cancer
#14
Zejun Fang, Aifen Lin, Jiaoe Chen, Xiaomin Zhang, Hong Liu, Hongzhang Li, Yanyan Hu, Xia Zhang, Jiangang Zhang, Lanlan Qiu, Lingming Mei, Jimin Shao, Xiang Chen
As the small subunit of Ribonucleotide reductase (RR), RRM2 displays a very important role in various critical cellular processes such as cell proliferation, DNA repair, and senescence, etc. Importantly, RRM2 functions like a tumor driver in most types of cancer but little is known about the regulatory mechanism of RRM2 in cancer development. In this study, we found that the cAMP responsive element binding protein 1 (CREB1) acted as a transcription factor of RRM2 gene in human colorectal cancer (CRC). CREB1 directly bound to the promoter of RRM2 gene and induced its transcriptional activation...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27764728/hpv31-utilizes-the-atr-chk1-pathway-to-maintain-elevated-rrm2-levels-and-a-replication-competent-environment-in-differentiating-keratinocytes
#15
Daniel C Anacker, Heather L Aloor, Caitlin N Shepard, Gina M Lenzi, Bryan A Johnson, Baek Kim, Cary A Moody
Productive replication of human papillomaviruses (HPV) is restricted to the uppermost layers of the differentiating epithelia. How HPV ensures an adequate supply of cellular substrates for viral DNA synthesis in a differentiating environment is unclear. Here, we demonstrate that HPV31 positive cells exhibit increased dNTP pools and levels of RRM2, a component of the ribonucleotide reductase (RNR) complex, which is required for de novo synthesis of dNTPs. RRM2 depletion blocks productive replication, suggesting RRM2 provides dNTPs for viral DNA synthesis in differentiating cells...
December 2016: Virology
https://www.readbyqxmd.com/read/27748721/precision-medicine-and-pancreatic-cancer-a-gemcitabine-pathway-approach
#16
James J Farrell, Jennifer Moughan, Jonathan L Wong, William F Regine, Paul Schaefer, Al B Benson, John S Macdonald, Xiyong Liu, Yun Yen, Raymond Lai, Zhong Zheng, Gerold Bepler, Chandan Guha, Hany Elsaleh
OBJECTIVES: There is a need for validated predictive markers of gemcitabine response to guide precision medicine treatment in pancreatic cancer. We previously validated human equilibrative nucleoside transporter 1 as a predictive marker of gemcitabine treatment response using Radiation Therapy Oncology Group 9704. Controversy exists about the predictive value of gemcitabine metabolism pathway biomarkers: deoxycytidine kinase (DCK), ribonucleotide reductase 1 (RRM1), RRM2, and p53R2. METHODS: Radiation Therapy Oncology Group 9704 prospectively randomized 538 patients after pancreatic resection to receive either 5-fluorouracil or gemcitabine...
November 2016: Pancreas
https://www.readbyqxmd.com/read/27725909/cell-cycle-dependent-rrm2-may-serve-as-proliferation-marker-and-pharmaceutical-target-in-adrenocortical-cancer
#17
Vince Kornél Grolmusz, Katalin Karászi, Tamás Micsik, Eszter Angéla Tóth, Katalin Mészáros, Gellért Karvaly, Gábor Barna, Péter Márton Szabó, Kornélia Baghy, János Matkó, Ilona Kovalszky, Miklós Tóth, Károly Rácz, Péter Igaz, Attila Patócs
Adrenocortical cancer (ACC) is a rare, but agressive malignancy with poor prognosis. Histopathological diagnosis is challenging and pharmacological options for treatment are limited. By the comparative reanalysis of the transcriptional malignancy signature with the cell cycle dependent transcriptional program of ACC, we aimed to identify novel biomarkers which may be used in the histopathological diagnosis and for the prediction of therapeutical response of ACC. Comparative reanalysis of publicly available microarray datasets included three earlier studies comparing transcriptional differences between ACC and benign adrenocortical adenoma (ACA) and one study presenting the cell cycle dependent gene expressional program of human ACC cell line NCI-H295R...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27670694/modeling-and-proposed-molecular-mechanism-of-hydroxyurea-through-docking-and-molecular-dynamic-simulation-to-curtail-the-action-of-ribonucleotide-reductase
#18
Maryam Iman, Zeynab Khansepid, Asghar Davood
BACKGROUND: Ribonucleotide Reductase (RNR) is an important anticancer chemotherapy target. It has main key role in DNA synthesis and cell growth. Therefore several RNR inhibitors, such as Hydroxyurea, have entered the clinical trials. Based on our proposed mechanism, radical site of RNR protein reacts with Hydroxyurea in which hydroxyurea is converted into its oxidized form compound III, and whereby the tyrosyl radical is converted into a normal tyrosine residue. OBJECTIVE: In this study, docking and molecular dynamics simulations were used for proposed molecular mechanism of Hydroxyurea in RNR inhibition as anticancer agent...
September 26, 2016: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/27649294/a-200-mev-uphill-thermodynamic-landscape-for-radical-transport-in-escherichia-coli-ribonucleotide-reductase-determined-using-fluorotyrosine-substituted-enzymes
#19
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 7, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27634056/nucleoside-analogue-triphosphates-allosterically-regulate-human-ribonucleotide-reductase-and-identify-chemical-determinants-that-drive-substrate-specificity
#20
Andrew J Knappenberger, Md Faiz Ahmad, Rajesh Viswanathan, Chris G Dealwis, Michael E Harris
Class I ribonucleotide reductase (RR) maintains balanced pools of deoxyribonucleotide substrates for DNA replication by converting ribonucleoside diphosphates (NDPs) to 2'-deoxyribonucleoside diphosphates (dNDPs). Binding of deoxynucleoside triphosphate (dNTP) effectors (ATP/dATP, dGTP, and dTTP) modulates the specificity of class I RR for CDP, UDP, ADP, and GDP substrates. Crystal structures of bacterial and eukaryotic RRs show that dNTP effectors and NDP substrates bind on either side of a flexible nine-amino acid loop (loop 2)...
October 3, 2016: Biochemistry
keyword
keyword
62090
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"