Genomes and Genes
Summary: Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
- Theodoropoulou S, Kolovou P, Morizane Y, Kayama M, Nicolaou F, Miller J, et al. Retinoblastoma cells are inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase. FASEB J. 2010;24:2620-30 pubmed publisher..Our results indicate that AICAR-induced activation of AMPK inhibits retinoblastoma cell growth. This is one of the first descriptions of a nonchemotherapeutic drug with low toxicity that may be effective in treating Rb patients. ..
- Suzuki J, Manola A, Murakami Y, Morizane Y, Takeuchi K, Kayama M, et al. Inhibitory effect of aminoimidazole carboxamide ribonucleotide (AICAR) on endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2011;52:6565-71 pubmed publisher..CONCLUSIONS. AICAR reduces systemic LPS susceptibility and attenuates intraocular inflammation in a rat EIU model by limiting infiltration of leukocytes, suppressing inflammatory mediators, and inhibiting the NF-?B pathway. ..
- McDonald J, Vaisman A, Kuban W, Goodman M, Woodgate R. Mechanisms employed by Escherichia coli to prevent ribonucleotide incorporation into genomic DNA by Pol V. PLoS Genet. 2012;8:e1003030 pubmed publisher..Our observations suggest that errant ribonucleotides incorporated by pol V can be tolerated in the E...
- Williams J, Clausen A, Nick McElhinny S, Watts B, Johansson E, Kunkel T. Proofreading of ribonucleotides inserted into DNA by yeast DNA polymerase É›. DNA Repair (Amst). 2012;11:649-56 pubmed publisher..exonuclease activity of Saccharomyces cerevisiae DNA polymerase É› (Pol É›) to proofread newly inserted ribonucleotides (rNMPs)...
- Woodard J, Joshi S, Viollet B, Hay N, Platanias L. AMPK as a therapeutic target in renal cell carcinoma. Cancer Biol Ther. 2010;10:1168-77 pubmed..Altogether, our studies demonstrate that AMPK plays critical regulatory roles in the regulation of growth of RCC cells and raise the prospect of future use of AMPK activators in the treatment of renal cell carcinoma in humans. ..
- Nick McElhinny S, Kumar D, Clark A, Watt D, Watts B, LundstrÃ¶m E, et al. Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol. 2010;6:774-81 pubmed publisher..However, ribonucleotide exclusion during DNA synthesis in vitro is imperfect. To determine whether ribonucleotides are incorporated during DNA replication in vivo, we substituted leucine or glycine for an active-site ..
- Williams J, Smith D, Marjavaara L, Lujan S, Chabes A, Kunkel T. Topoisomerase 1-mediated removal of ribonucleotides from nascent leading-strand DNA. Mol Cell. 2013;49:1010-5 pubmed publisherRNase H2-dependent ribonucleotide excision repair (RER) removes ribonucleotides incorporated during DNA replication...
- Ferraro P, Franzolin E, Pontarin G, Reichard P, Bianchi V. Quantitation of cellular deoxynucleoside triphosphates. Nucleic Acids Res. 2010;38:e85 pubmed publisher..We suggest that in some earlier reports ribonucleotide incorporation may have caused too high values for dGTP and dCTP. ..
- Murina V, Lekontseva N, Nikulin A. Hfq binds ribonucleotides in three different RNA-binding sites. Acta Crystallogr D Biol Crystallogr. 2013;69:1504-13 pubmed publisher..In this work, the ability of various ribonucleotides to form complexes with Hfq from Pseudomonas aeruginosa has been tested using X-ray crystallography...
- Kennedy E, Amie S, Bambara R, Kim B. Frequent incorporation of ribonucleotides during HIV-1 reverse transcription and their attenuated repair in macrophages. J Biol Chem. 2012;287:14280-8 pubmed publisher..Most importantly, the frequent incorporation of rNMPs makes them an ideal candidate for development of a new class of HIV RT inhibitors. ..
- Wang S, Zhang M, Liang B, Xu J, Xie Z, Liu C, et al. AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes. Circ Res. 2010;106:1117-28 pubmed publisher..We conclude that AMPKalpha2 functions as a physiological suppressor of NAD(P)H oxidase and ROS production in endothelial cells. In this way, AMPK maintains the nonatherogenic and noninflammatory phenotype of endothelial cells. ..
- Lantier L, Mounier R, Leclerc J, Pende M, Foretz M, Viollet B. Coordinated maintenance of muscle cell size control by AMP-activated protein kinase. FASEB J. 2010;24:3555-61 pubmed publisher..Our results uncover the role of AMPK in the maintenance of muscle cell size control and highlight the crosstalk between AMPK and mTOR/p70S6K signaling pathways coordinating a metabolic checkpoint on cell growth. ..
- Vichaiwong K, Purohit S, An D, Toyoda T, Jessen N, Hirshman M, et al. Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle. Biochem J. 2010;431:311-20 pubmed publisher..AMPK and Akt regulate TBC1D1 phosphorylation, but there must be additional upstream kinases that mediate TBC1D1 phosphorylation in skeletal muscle...
- Ghodgaonkar M, Lazzaro F, Olivera Pimentel M, Artola Borán M, Cejka P, Reijns M, et al. Ribonucleotides misincorporated into DNA act as strand-discrimination signals in eukaryotic mismatch repair. Mol Cell. 2013;50:323-32 pubmed publisher..We therefore propose that ribonucleotides misincoporated during DNA replication serve as physiological markers of the nascent DNA strand.
- Yao N, Schroeder J, Yurieva O, Simmons L, O Donnell M. Cost of rNTP/dNTP pool imbalance at the replication fork. Proc Natl Acad Sci U S A. 2013;110:12942-7 pubmed publisher..Here we demonstrate that Bacillus subtilis incorporates rNMPs in vivo, that RNase HII plays a role in their removal, and the RNase HII gene deletion enhances mutagenesis, suggesting a possible role of incorporated rNMPs in MMR...
- Reijns M, Rabe B, Rigby R, Mill P, Astell K, Lettice L, et al. Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development. Cell. 2012;149:1008-22 pubmed publisherThe presence of ribonucleotides in genomic DNA is undesirable given their increased susceptibility to hydrolysis. Ribonuclease (RNase) H enzymes that recognize and process such embedded ribonucleotides are present in all domains of life...
- Suzuki J, Yoshimura T, Simeonova M, Takeuchi K, Murakami Y, Morizane Y, et al. Aminoimidazole carboxamide ribonucleotide ameliorates experimental autoimmune uveitis. Invest Ophthalmol Vis Sci. 2012;53:4158-69 pubmed publisher..AICAR attenuates EAU by preventing generation of Ag-specific Th1 and Th17 cells. Impaired DC maturation may be an underlying mechanism for this anti-inflammatory effect observed with AICAR. ..
- Vaisman A, Kuban W, McDonald J, Karata K, Yang W, Goodman M, et al. Critical amino acids in Escherichia coli UmuC responsible for sugar discrimination and base-substitution fidelity. Nucleic Acids Res. 2012;40:6144-57 pubmed..Remarkably, under these conditions, wild-type pol V Mut efficiently incorporates ribonucleotides into DNA...
- Lujan S, Williams J, Clausen A, Clark A, Kunkel T. Ribonucleotides are signals for mismatch repair of leading-strand replication errors. Mol Cell. 2013;50:437-43 pubmed publisher..mismatch repair in Saccharomyces cerevisiae is reduced by inactivating RNase H2, which nicks DNA containing ribonucleotides incorporated during replication...
- Kuban W, Vaisman A, McDonald J, Karata K, Yang W, Goodman M, et al. Escherichia coli UmuC active site mutants: effects on translesion DNA synthesis, mutagenesis and cell survival. DNA Repair (Amst). 2012;11:726-32 pubmed publisher..V (pol V/UmuD(2)'C) is a low-fidelity DNA polymerase that has recently been shown to avidly incorporate ribonucleotides (rNTPs) into undamaged DNA...
- Pauly M, Daussin F, Burelle Y, Li T, Godin R, Fauconnier J, et al. AMPK activation stimulates autophagy and ameliorates muscular dystrophy in the mdx mouse diaphragm. Am J Pathol. 2012;181:583-92 pubmed publisher..These findings suggest that agonists of AMPK and other inducers of the autophagy-mitophagy pathway can help to promote the elimination of defective mitochondria and may thus serve as useful therapeutic agents in DMD. ..
- Viscomi C, Bottani E, Civiletto G, Cerutti R, Moggio M, Fagiolari G, et al. In vivo correction of COX deficiency by activation of the AMPK/PGC-1? axis. Cell Metab. 2011;14:80-90 pubmed publisher..These results open new perspectives for therapy of mitochondrial disease. ..
- Vaisman A, McDonald J, Huston D, Kuban W, Liu L, Van Houten B, et al. Removal of misincorporated ribonucleotides from prokaryotic genomes: an unexpected role for nucleotide excision repair. PLoS Genet. 2013;9:e1003878 pubmed publisherStringent steric exclusion mechanisms limit the misincorporation of ribonucleotides by high-fidelity DNA polymerases into genomic DNA...
- Cho J, Kim N, Li Y, Jinks Robertson S. Two distinct mechanisms of Topoisomerase 1-dependent mutagenesis in yeast. DNA Repair (Amst). 2013;12:205-11 pubmed publisher..Data suggest a novel model in which rNMP-dependent hotspots are generated by sequential Top1 reactions and are consistent with rNMP-independent hotspots reflecting processing of a trapped Top1 cleavage complex. ..
- Wang W, Wu E, Hellinga H, Beese L. Structural factors that determine selectivity of a high fidelity DNA polymerase for deoxy-, dideoxy-, and ribonucleotides. J Biol Chem. 2012;287:28215-26 pubmed publisher..This mechanism may extend also to base pair discrimination. ..
- Kirouac K, Suo Z, Ling H. Structural mechanism of ribonucleotide discrimination by a Y-family DNA polymerase. J Mol Biol. 2011;407:382-90 pubmed publisherThe ability of DNA polymerases to differentiate between ribonucleotides and deoxribonucleotides is fundamental to the accurate replication and maintenance of an organism's genome...
- Kasahara Y, Irisawa Y, Ozaki H, Obika S, Kuwahara M. 2',4'-BNA/LNA aptamers: CE-SELEX using a DNA-based library of full-length 2'-O,4'-C-methylene-bridged/linked bicyclic ribonucleotides. Bioorg Med Chem Lett. 2013;23:1288-92 pubmed publisherDNA-based aptamers that contain 2'-O,4'-C-methylene-bridged/linked bicyclic ribonucleotides (B/L nucleotides) over the entire length were successfully obtained using a capillary electrophoresis systematic evolution of ligands by ..
- Kasiviswanathan R, Copeland W. Ribonucleotide discrimination and reverse transcription by the human mitochondrial DNA polymerase. J Biol Chem. 2011;286:31490-500 pubmed publisherDuring DNA synthesis, DNA polymerases must select against ribonucleotides, present at much higher levels compared with deoxyribonucleotides...
- Zhang N, Zhang S, Szostak J. Activated ribonucleotides undergo a sugar pucker switch upon binding to a single-stranded RNA template. J Am Chem Soc. 2012;134:3691-4 pubmed publisher..We hypothesized that ribonucleotides undergo a switch in sugar pucker upon binding to an A-type template and that this conformational switch ..
- Hunter R, Treebak J, Wojtaszewski J, Sakamoto K. Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Diabetes. 2011;60:766-74 pubmed publisher..We provide genetic evidence that AMPK activation promotes muscle glycogen accumulation by allosteric activation of GS through an increase in glucose uptake and subsequent rise in cellular [G6P]. ..
- Chen M, Shen W, Yang Y, Wu X, Gu J, Lu P. Activation of AMP-activated protein kinase is involved in vincristine-induced cell apoptosis in B16 melanoma cell. J Cell Physiol. 2011;226:1915-25 pubmed publisher..We suggest that combining AMPK activator AICAR with vincristine may have potential to be used as a new therapeutic intervention against melanoma. ..
- Watt D, Johansson E, Burgers P, Kunkel T. Replication of ribonucleotide-containing DNA templates by yeast replicative polymerases. DNA Repair (Amst). 2011;10:897-902 pubmed publisherThe major replicative DNA polymerases of S. cerevisiae (Pols ?, ?, and ?) incorporate substantial numbers of ribonucleotides into DNA during DNA synthesis...
- Martín M, Garcia Ortiz M, Esteban V, Blanco L. Ribonucleotides and manganese ions improve non-homologous end joining by human Pol?. Nucleic Acids Res. 2013;41:2428-36 pubmed publisher..similarity between Polµ and terminal deoxynucleotidyl transferase (TdT) is their promiscuity in using ribonucleotides (NTPs), whose physiological significance is presently unknown...
- Shen Y, Koh K, Weiss B, Storici F. Mispaired rNMPs in DNA are mutagenic and are targets of mismatch repair and RNases H. Nat Struct Mol Biol. 2011;19:98-104 pubmed publisher..In the absence of mismatch repair and RNases H, ribonucleotide-driven gene modification increased by a factor of 47 in yeast and 77,000 in E. coli. ..
- Yarus M. Darwinian behavior in a cold, sporadically fed pool of ribonucleotides. Astrobiology. 2012;12:870-83 pubmed publisher..Finally, analysis points to particular data now needed to refine the hypothesis. Accordingly, a kinetically explicit chemical hypothesis for a terran IDA can be justified, and informative experiments seem readily accessible. ..
- Hiller B, Achleitner M, Glage S, Naumann R, Behrendt R, Roers A. Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity. J Exp Med. 2012;209:1419-26 pubmed publisher..RNase H2-deficient cells featured an increased genomic ribonucleotide load, suggesting that unrepaired ribonucleotides trigger the DNA damage response in these cells...
- Goirand F, Solar M, Athea Y, Viollet B, Mateo P, Fortin D, et al. Activation of AMP kinase alpha1 subunit induces aortic vasorelaxation in mice. J Physiol. 2007;581:1163-71 pubmed..Taken together, the results show that activation of AMPKalpha1 but not AMPKalpha2 is able to induce aortic relaxation in mice, in an endothelium- and eNOS-independent manner. ..
- Thomson D, Herway S, Fillmore N, Kim H, Brown J, Barrow J, et al. AMP-activated protein kinase phosphorylates transcription factors of the CREB family. J Appl Physiol (1985). 2008;104:429-38 pubmed..We conclude that CREB and related proteins are direct downstream targets for AMPK and are therefore likely involved in mediating some effects of AMPK on expression of genes having a CRE in their promoters. ..
- Lihn A, Pedersen S, Lund S, Richelsen B. The anti-diabetic AMPK activator AICAR reduces IL-6 and IL-8 in human adipose tissue and skeletal muscle cells. Mol Cell Endocrinol. 2008;292:36-41 pubmed publisher..In conclusion, AICAR inhibits the production of IL-6 and IL-8 human adipose tissue and in skeletal muscle cells. We suggest that decreased cytokine production might play a role for the AICAR-induced increase in insulin sensitivity. ..
- Anthony N, Gaidhu M, Ceddia R. Regulation of visceral and subcutaneous adipocyte lipolysis by acute AICAR-induced AMPK activation. Obesity (Silver Spring). 2009;17:1312-7 pubmed publisher..In summary, despite different fat depots eliciting distinct rates of lipolysis, acute AICAR-induced AMPK activation suppressed HSL phosphorylation/activation and exerted similar antilipolytic effects on both VC and SC adipocytes. ..
- Maarbjerg S, Jørgensen S, Rose A, Jeppesen J, Jensen T, Treebak J, et al. Genetic impairment of AMPKalpha2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice. Am J Physiol Endocrinol Metab. 2009;297:E924-34 pubmed publisher..Collectively, these findings suggest that AMPKalpha2 signaling is not essential in regulating glucose uptake in mouse skeletal muscle during treadmill exercise and that other mechanisms play a central role. ..
- Narkar V, Downes M, Yu R, Embler E, Wang Y, Banayo E, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008;134:405-15 pubmed publisher..These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise. ..
- Sengupta T, Leclerc G, Hsieh Kinser T, Leclerc G, Singh I, Barredo J. Cytotoxic effect of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: implication for targeted therapy. Mol Cancer. 2007;6:46 pubmed..Therefore, activation of AMPK by AICAR represents a novel approach to targeted therapy, and suggests a role for AICAR in combination therapy with inhibitors of the PI3K/Akt/mTOR pathways for the treatment of childhood in ALL. ..
- Wong A, Howie J, Petrie J, Lang C. AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease. Clin Sci (Lond). 2009;116:607-20 pubmed publisher..Increased understanding of the beneficial effects of AMPK activation provides the rationale for targeting AMPK in the development of new therapeutic strategies for cardiometabolic disease. ..
- Qiang W, Weiqiang K, Qing Z, Pengju Z, Yi L. Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKalpha. Exp Mol Med. 2007;39:535-43 pubmed..In conclusion, aging-related insulin resistance is associated with impaired AMPKalpha activity and could be ameliorated by AICAR, thus indicating a possible role of AMPK in aging-induced insulin resistance. ..
- Dzamko N, Schertzer J, Ryall J, Steel R, Macaulay S, Wee S, et al. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation. J Physiol. 2008;586:5819-31 pubmed publisher..These data demonstrate that AMPK is not essential for the regulation of fatty acid oxidation by AICAR or muscle contraction. ..
- Woollhead A, Sivagnanasundaram J, Kalsi K, Pucovsky V, Pellatt L, Scott J, et al. Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells. Br J Pharmacol. 2007;151:1204-15 pubmed
- Nakashima K, Yakabe Y. AMPK activation stimulates myofibrillar protein degradation and expression of atrophy-related ubiquitin ligases by increasing FOXO transcription factors in C2C12 myotubes. Biosci Biotechnol Biochem. 2007;71:1650-6 pubmed..These results indicate that activation of AMPK stimulates myofibrillar protein degradation through the expression of atrogin-1/MAFbx and MuRF1 by increasing FOXO transcription factors in skeletal muscles. ..
- Peairs A, Radjavi A, Davis S, Li L, Ahmed A, Giri S, et al. Activation of AMPK inhibits inflammation in MRL/lpr mouse mesangial cells. Clin Exp Immunol. 2009;156:542-51 pubmed publisher..Taken together, these observations suggest that AICAR inhibits LPS/IFN-gamma-induced Akt phosphorylation through AMPK activation and may serve as a potential therapeutic target in inflammatory diseases...
- Robertson T, Mustard K, Lewis T, Clark J, Wyatt C, Blanco E, et al. AMP-activated protein kinase and hypoxic pulmonary vasoconstriction. Eur J Pharmacol. 2008;595:39-43 pubmed publisher..The results of the present study are consistent with the activation of AMPK being a key event in the initiation of the contractile response of pulmonary arteries to acute hypoxia. ..
- Gaidhu M, Fediuc S, Anthony N, So M, Mirpourian M, Perry R, et al. Prolonged AICAR-induced AMP-kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. J Lipid Res. 2009;50:704-15 pubmed publisher..Additionally, we show novel time-dependent effects of AICAR-induced AMPK activation on lipolysis, which involves antagonistic modulation of HSL and ATGL. ..
- Powner M, Gerland B, Sutherland J. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature. 2009;459:239-42 pubmed publisher..In particular, although there has been some success demonstrating that 'activated' ribonucleotides can polymerize to form RNA, it is far from obvious how such ribonucleotides could have formed from their ..
- Tzvetkova S, Kluger R. Biomimetic aminoacylation of ribonucleotides and RNA with aminoacyl phosphate esters and lanthanum salts. J Am Chem Soc. 2007;129:15848-54 pubmed..This does not occur if the 3'-terminus is converted to the dialdehyde by reaction with periodate. ..
- Canto C, Gerhart Hines Z, Feige J, Lagouge M, Noriega L, Milne J, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009;458:1056-60 pubmed publisher..The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism. ..
- Mace O, Woollhead A, Baines D. AICAR activates AMPK and alters PIP2 association with the epithelial sodium channel ENaC to inhibit Na+ transport in H441 lung epithelial cells. J Physiol. 2008;586:4541-57 pubmed publisher..Thus, when PIP(2)-ENaC subunit interactions were compromised, ENaC protein retrieval was initiated, indicating that AMPK can modulate ENaC P(o) and N. ..
- Taylor E, An D, Kramer H, Yu H, Fujii N, Roeckl K, et al. Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle. J Biol Chem. 2008;283:9787-96 pubmed publisher..TBC1D1 is a major PAS immunoreactive protein in skeletal muscle that is phosphorylated in vivo by insulin, AICAR, and contraction. Both Akt and AMPK phosphorylate TBC1D1, but AMPK may be the more robust regulator. ..
- Guo D, Hildebrandt I, Prins R, Soto H, Mazzotta M, Dang J, et al. The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis. Proc Natl Acad Sci U S A. 2009;106:12932-7 pubmed publisher..These results suggest a mechanism by which AICAR inhibits the proliferation of EGFRvIII expressing glioblastomas and point toward a potential therapeutic strategy for targeting EGFR-activated cancers. ..
- Kim J, Kim Y, Lee I, Kim J, Kang Y, Park S. AMP-activated protein kinase activation by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) inhibits palmitate-induced endothelial cell apoptosis through reactive oxygen species suppression. J Pharmacol Sci. 2008;106:394-403 pubmed..These data suggest that the activation of AMPK inhibits palmitate-induced endothelial cell apoptosis through the suppression of ROS generation, and UCP-2 may be one of possible mediators of the antioxidative effect of AMPK. ..