• We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. (nature.com)
  • RNR contains two subunits: ribonucleotide reductase subunit M1 (RRM1) and M2 (RRM2) [ 16 ]. (nature.com)
  • This phenotype reflected unanticipated regulation of global replication by IGF1 mediated via AKT, MEK/ERK, and JUN to influence expression of ribonucleotide reductase (RNR) subunit RRM2. (ox.ac.uk)
  • Of interest was the increased expression of ribonucleotide reductase regulatory subunit M2 (RRM2), which we found to regulate dGTP and dCTP production vital for DNA damage response during TMZ therapy . (bvsalud.org)
  • We then identified ribonucleotide reductase M2 (RRM2), the iron-dependent subunit of ribonucleotide reductase (RNR), as one mediator of iron chelator toxicity in Ewing sarcoma cells. (oncotarget.com)
  • It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21 Cip/Waf and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. (nature.com)
  • The dATP increase results in inhibition of ribonucleotide reductase and underproduction of other deoxyribonucleotides. (msdmanuals.com)
  • The catalytic subunit of an anaerobic ribonucleotide reductase: What binds where? (lu.se)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Ribonucleotide Reductase M1 (RRM1) in tissue homogenates, cell lysates and other biological fluids. (allelisakits.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Ribonucleotide Reductase M1 (RRM1) in samples from tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (allelisakits.com)
  • Description: A sandwich quantitative ELISA assay kit for detection of Mouse Ribonucleotide Reductase M1 (RRM1) in samples from tissue homogenates or other biological fluids. (allelisakits.com)
  • Ribonucleotide reductases (RNRs) are essential for DNA synthesis in most organisms. (diva-portal.org)
  • Bacterial ribonucleotide reductases (RNRs) play a significant role in the formation of dNTPs and their expression is normally regulated with the transcription factors NrdR and Hair. (immune-source.com)
  • Ribonucleotide reductases (RNRs) are essential enzymes for all life by virtue of their central role in the de novo synthesis of deoxyribonucleotides, the building blocks for DNA synthesis. (lu.se)
  • Ribonucleotide reductase regulatory subunit M2 drives glioblastoma TMZ resistance through modulation of dNTP production. (bvsalud.org)
  • Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. (wikipedia.org)
  • The enzyme ribonucleotide reductase (RNR) catalyzes the de novo synthesis of dNDPs. (wikipedia.org)
  • c) activity is stimulated by thioredoxin and ATP and is inhibited by dATP, showing that as in the mammalian enzyme, the plant ribonucleotide reductase seems to be allosterically regulated by positive (ATP) and negative (dATP) effectors. (hal.science)
  • Deoxy-ATP (dATP) can reach toxic levels that inhibit ribonucleotide reductase, an enzyme essential for synthesis of DNA precursors. (medscape.com)
  • It is a pyrimidine antimetabolite that nhibits DNA polymerase and ribonucleotide reductase, which in turn inhibit DNA synthesis. (medscape.com)
  • Protein activation and expression were analysed by western blotting, deoxyribonucleoside triphosphate levels by HPLC, ribonucleotide reductase activity by 14 C-cytidine incorporation into nascent DNA and cell-cycle distribution by FACS. (nature.com)
  • Protein R1 is the proper reductase as it contains, in the substrate binding site, the reducing active cysteine pair. (hal.science)
  • A novel approach to study PCET reactions illustrates the importance of solvent-slaved protein motions in copper nitrite reductase catalysis. (rsc.org)
  • The data show that ERCC5, encoding Xeroderma pigmentosum protein G (XPG), essential for DNA excision repair, and ribonucleotide reductase subunit M1 (RNRM1), encoding a gene necessary for providing the nucleotides needed for DNA repair, were down-regulated in cells treated with diazinon. (cdc.gov)
  • Micro-array analysis showed increased expression of ribonucleotide reductase (RR) subunits M1 and M2 as confirmed by real time PCR analysis (28- and 2.7-fold, respectively). (amsterdamumc.org)
  • This study identifies regulation of ribonucleotide reductase function and dNTP supply by IGFs and demonstrates that IGF axis blockade induces replication stress and reciprocal codependence on ATM. (ox.ac.uk)
  • An active ribonucleotide reductase from Arabidopsis thaliana cloning, expression and characterization of the large subunit. (hal.science)
  • Stubbe, JA & Seyedsayamdost, MR 2019, ' Discovery of a New Class i Ribonucleotide Reductase with an Essential DOPA Radical and NO Metal as an Initiator of Long-Range Radical Transfer ', Biochemistry , vol. 58, no. 6, pp. 435-437. (princeton.edu)
  • The ribonucleotide reductase inhibitor hydroxyurea exhibits potent synergism, even at low, non-cytotoxic concentrations, with the anti-HIV-1 dideoxynucleoside 2',3'-dideoxyinosine, bringing about failure of HIV DNA synthesis and, thus, of HIV replication. (tmu.edu.tw)
  • It also inhibits dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyl transferase (GARFT). (scirp.org)
  • dGTP inhibits ribonucleotide reductase, which is needed for synthesis of deoxynucleotides. (medscape.com)
  • Deletion of ribonucleotide reductase (RNR) genes in E. coli . (elifesciences.org)
  • RT-PCR indicates that ribonucleotide reductase (RNR) genes are not expressed in ∆RNR. (elifesciences.org)
  • By selecting organisms resistant to the novel inhibitors and sequencing their genomes, we identified a new therapeutic target, the class Ia ribonucleotide reductase (RNR). (elifesciences.org)
  • 60 known mutations) results in accumulation of adenosine , which is converted to its ribonucleotide and deoxyribonucleotide (dATP) forms by cellular kinases. (msdmanuals.com)
  • The authors present two small molecules that specifically target the essential ribonucleotide reductase of the causative agent of gonorrhea. (elifesciences.org)
  • Description: A sandwich ELISA kit for detection of Ribonucleotide Reductase M1 from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (allelisakits.com)
  • Studying seven cases of profound mtDNA depletion (1-2% residual mtDNA in muscle) in four unrelated families, we have found nonsense, missense and splice-site mutations and in-frame deletions of the RRM2B gene, encoding the cytosolic p53-inducible ribonucleotide reductase small subunit. (nih.gov)
  • This phenotype reflected unanticipated regulation of global replication by IGF1 mediated via AKT, MEK/ERK, and JUN to influence expression of ribonucleotide reductase (RNR) subunit RRM2. (ox.ac.uk)
  • We recently reported that genetic or pharmacological inhibition of insulin-like growth factor receptor (IGF-1R) slows DNA replication and induces replication stress by downregulating the regulatory subunit RRM2 of ribonucleotide reductase, perturbing deoxynucleotide triphosphate (dNTP) supply. (nature.com)
  • RNR contains two subunits: ribonucleotide reductase subunit M1 (RRM1) and M2 (RRM2) [ 16 ]. (nature.com)
  • An active ribonucleotide reductase from Arabidopsis thaliana cloning, expression and characterization of the large subunit. (hal.science)
  • Ribonucleotide reductase M2 (RRM2) is a small subunit in ribonucleotide reductases , which participate in nucleotide metabolism and catalyze the conversion of nucleotides to deoxynucleotides, maintaining the dNTP pools for DNA biosynthesis , repair, and replication. (bvsalud.org)
  • The diiron(II) cluster in the R2 subunit of Escherichia coli ribonucleotide reductase (RNR) activates oxygen to generate a μ-oxodiiron(III) cluster and the stable tyrosyl radical that is critical for the conversion of ribonucleotides to deoxyribonucleotides. (psu.edu)
  • 10. ATR-CHK1-E2F3 signaling transactivates human ribonucleotide reductase small subunit M2 for DNA repair induced by the chemical carcinogen MNNG. (nih.gov)
  • 13. Ribonucleotide Reductase Requires Subunit Switching in Hypoxia to Maintain DNA Replication. (nih.gov)
  • 14. A Single Conserved Residue Mediates Binding of the Ribonucleotide Reductase Catalytic Subunit RRM1 to RRM2 and Is Essential for Mouse Development. (nih.gov)
  • This gene encodes the small subunit of a p53-inducible ribonucleotide reductase. (antikoerper-online.de)
  • The data show that ERCC5, encoding Xeroderma pigmentosum protein G (XPG), essential for DNA excision repair, and ribonucleotide reductase subunit M1 (RNRM1), encoding a gene necessary for providing the nucleotides needed for DNA repair, were down-regulated in cells treated with diazinon. (cdc.gov)
  • 12. mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer. (nih.gov)
  • In this talk, the conformational gymnastics involved in ribonucleotide reduction will be considered. (nih.gov)
  • The three-dimensional structure of mammalian ribonucleotide reductase protein R2 reveals a more-accessible iron-radical site than Escherichia coli R2. (expasy.org)
  • The invariant active site residue Glu441 in protein R1 of ribonucleotide reductase from Escherichia coli has been engineered to alanine, aspartic acid, and glutamic acid. (proteopedia.org)
  • A new mechanism-based radical intermediate in a mutant R1 protein affecting the catalytically essential Glu441 in Escherichia coli ribonucleotide reductase. (proteopedia.org)
  • This study identifies regulation of ribonucleotide reductase function and dNTP supply by IGFs and demonstrates that IGF axis blockade induces replication stress and reciprocal codependence on ATM. (ox.ac.uk)
  • Ribonucleoside diphosphate reductase (EC 1.17.4.1) (RR) is a potential target for antineoplastic agents due to its crucial role in DNA replication and repair. (tmu.edu.tw)
  • P.229 right column bottom paragraph: 'The mechanism for replication arrest when RNR [ribonucleotide reductase] is inhibited remains unknown. (harvard.edu)
  • If RNR inhibition resulted in significant expansion of the rNTP pools, it is possible that an increased rNTP/dNTP ratio might result in misincorporation of ribonucleotides into DNA and thereby trigger a replication arrest. (harvard.edu)
  • 2. Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response. (nih.gov)
  • His current research interests focus on the identification of new antimicrobial therapies and unravel the molecular mechanism underlying the transcripcional regulation of bacterial ribonucleotide reductase genes. (ibecbarcelona.eu)
  • 7. Cross-species genomic and functional analyses identify a combination therapy using a CHK1 inhibitor and a ribonucleotide reductase inhibitor to treat triple-negative breast cancer. (nih.gov)
  • Ribonucleotide reductase and mitochondrial DNA synthesis. (nih.gov)
  • Ribonucleotide reductase (RNR) is an essential holoenzyme required for de novo synthesis of dNTPs. (microbialcell.com)
  • Ribonucleotide reductase (RNR) is a conserved holoenzyme required for de novo synthesis of dNTPs, the building blocks of DNA [1] . (microbialcell.com)
  • dGTP inhibits ribonucleotide reductase, which is needed for synthesis of deoxynucleotides. (medscape.com)
  • 1. A functional approach reveals a genetic and physical interaction between ribonucleotide reductase and CHK1 in mammalian cells. (nih.gov)
  • Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade " published in eLife Digest Oct. 4. (lightsources.org)
  • The tyrosyl free radical in ribonucleotide reductase. (nih.gov)
  • 2009. E2F4 and ribonucleotide reductase mediate S-phase arrest in colon cancer cells treated with chlorophyllin. . (oregonstate.edu)
  • Ribonucleotide reductase (RNR) and pyruvate formate lyase (PFL) are structurally similar and are thought to have diverged from a common ancestral domain. (nih.gov)
  • Serum ribonucleotide reductase M2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B patients. (amedeo.com)