Genomes and Genes
Summary: Uracil nucleotides which contain deoxyribose as the sugar moiety.
- Wilson P, Fazzone W, LaBonte M, Lenz H, Ladner R. Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009;37:78-95 pubmed publisher..Furthermore, these studies provide the first evidence of a direct transcriptional link between the essential enzyme dUTPase and the tumor suppressor p53. ..
- Nord J, Kiefer M, Adolph H, Zeppezauer M, Nyman P. Transient kinetics of ligand binding and role of the C-terminus in the dUTPase from equine infectious anemia virus. FEBS Lett. 2000;472:312-6 pubmed..We conclude that the flexible C-terminus is not a prerequisite for substrate binding, but indispensable for catalysis...
- Myllykallio H, Lipowski G, Leduc D, Filee J, Forterre P, Liebl U. An alternative flavin-dependent mechanism for thymidylate synthesis. Science. 2002;297:105-7 pubmed publisher..Our findings reveal complexity in the evolution of thymidine in present-day DNA. Because ThyX proteins are found in many pathogenic microbes, they present a previously uncharacterized target for antimicrobial compounds...
- Hogrefe H, Hansen C, Scott B, Nielson K. Archaeal dUTPase enhances PCR amplifications with archaeal DNA polymerases by preventing dUTP incorporation. Proc Natl Acad Sci U S A. 2002;99:596-601 pubmed publisher..In vivo, archaeal dUTPases may play an essential role in preventing dUTP incorporation and inhibition of DNA synthesis by family B DNA polymerases...
- Lee S, Sidorov A, Gourlain T, Mignet N, Thorpe S, Brazier J, et al. Enhancing the catalytic repertoire of nucleic acids: a systematic study of linker length and rigidity. Nucleic Acids Res. 2001;29:1565-73 pubmed..The incorporation of these analogues during PCR has been confirmed by inhibition of restriction enzyme digestion using XBAI and by mass spectrometry of the PCR products. ..
- Prasad G, Stura E, Elder J, Stout C. Structures of feline immunodeficiency virus dUTP pyrophosphatase and its nucleotide complexes in three crystal forms. Acta Crystallogr D Biol Crystallogr. 2000;56:1100-9 pubmed..In particular, the alpha-beta phosphodiester adopts an unfavorable eclipsed conformation in the presence of the P-loop. This conformation may be relevant to the mechanism of alpha-beta phosphodiester bond cleavage. ..
- Sampathkumar P, Turley S, Ulmer J, Rhie H, Sibley C, Hol W. Structure of the Mycobacterium tuberculosis flavin dependent thymidylate synthase (MtbThyX) at 2.0A resolution. J Mol Biol. 2005;352:1091-104 pubmed..Structure-based mutational studies have revealed a critical role played by residues Lys165 and Arg168 in ThyX activity, possibly by governing access to the carbon atom to be methylated of a totally buried substrate dUMP. ..
- Held H, Benner S. Challenging artificial genetic systems: thymidine analogs with 5-position sulfur functionality. Nucleic Acids Res. 2002;30:3857-69 pubmed..This remains curious, as the ability of the polymerase to replicate natural DNA with high fidelity and its propensity to exclude unnatural analogs are presumed to be correlated. ..
- Persson T, Larsson G, Nyman P. Synthesis of 2'-deoxyuridine 5'-(alpha,beta-imido) triphosphate: a substrate analogue and potent inhibitor of dUTPase. Bioorg Med Chem. 1996;4:553-6 pubmed
- Carreras C, Santi D. The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem. 1995;64:721-62 pubmed..Included is a discussion of available sources and assays for TS, a description of the enzyme's chemical mechanism and crystal structure, and a summary of data obtained from mutagenesis experiments. ..
- García Nafría J, Timm J, Harrison C, Turkenburg J, Wilson K. Tying down the arm in Bacillus dUTPase: structure and mechanism. Acta Crystallogr D Biol Crystallogr. 2013;69:1367-80 pubmed publisher..The enzyme mechanism is reviewed using the present and previous crystal structures as snapshots along the reaction coordinate. ..
- Fischer J, Muller Weeks S, CARADONNA S. Fluorodeoxyuridine modulates cellular expression of the DNA base excision repair enzyme uracil-DNA glycosylase. Cancer Res. 2006;66:8829-37 pubmed
- Kajimoto S, Horie M, Manabe H, Masuda Y, Shibayama Imazu T, Nakajo S, et al. A tyrosine kinase inhibitor, beta-hydroxyisovalerylshikonin, induced apoptosis in human lung cancer DMS114 cells through reduction of dUTP nucleotidohydrolase activity. Biochim Biophys Acta. 2008;1782:41-50 pubmed..These results suggest that dUTPase activity is one of the crucial factors involved in apoptotic cell death in lung cancer cells. ..
- Varga B, Barab s O, Tak cs E, Nagy N, Nagy P, V rtessy B. Active site of mycobacterial dUTPase: structural characteristics and a built-in sensor. Biochem Biophys Res Commun. 2008;373:8-13 pubmed publisher..A robust continuous activity assay for kinetic screening is proposed...
- Persson R, Cedergren Zeppezauer E, Wilson K. Homotrimeric dUTPases; structural solutions for specific recognition and hydrolysis of dUTP. Curr Protein Pept Sci. 2001;2:287-300 pubmed..In this review the structural arrangement of the homotrimeric dUTPases is discussed in the context of active site geometry, achievement of specificity and subunit interactions. ..
- Watanabe T, Bando T, Xu Y, Tashiro R, Sugiyama H. Efficient generation of 2'-deoxyuridin-5-yl at 5'-(G/C)AA(X)U(X)U-3' (X = Br, I) sequences in duplex DNA under UV irradiation. J Am Chem Soc. 2005;127:44-5 pubmed..These observations will be useful in studying the molecular basis of the sequence-dependent DNA-damaging process in UV-irradiated 5-halouracil-containing DNA. ..
- Chanama M, Chitnumsub P, Yuthavong Y. Subunit complementation of thymidylate synthase in Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase. Mol Biochem Parasitol. 2005;139:83-90 pubmed..falciparum DHFR-TS. ..
- Dabrowski S, Kiaer Ahring B. Cloning, expression, and purification of the His6-tagged hyper-thermostable dUTPase from Pyrococcus woesei in Escherichia coli: application in PCR. Protein Expr Purif. 2003;31:72-8 pubmed..We observed that the thermostable His(6)-tagged Pwo dUTPase used for the polymerase chain reaction with P. woesei DNA polymerase improves the efficiency of PCR and it allows for amplification of longer targets...
- Wlassoff W, King G. Ferrocene conjugates of dUTP for enzymatic redox labelling of DNA. Nucleic Acids Res. 2002;30:e58 pubmed..The availability of simple and effective enzymatic labelling strategies should promote the further development of electrochemical detection in nucleic acid analysis. ..
- Horvath A, Beck Z, Bardos T, Dunn J, Aradi J. Effect of the extent of thiolation and introduction of phosphorothioate internucleotide linkages on the anti-HIV activity of Suligovir [(s4dU)35]. Bioorg Med Chem Lett. 2006;16:5321-3 pubmed..We found that the decreased thiolated nucleotide content decreases the anti-HIV potency of the compound and the introduction of phosphorothioate linkages does not improve its antiviral activity. ..
- Litos I, Emmanouilidou E, Glynou K, Laios E, Ioannou P, Christopoulos T, et al. Rapid genotyping of CYP2D6, CYP2C19 and TPMT polymorphisms by primer extension reaction in a dipstick format. Anal Bioanal Chem. 2007;389:1849-57 pubmed..Patient samples (76 variants in total) were genotyped and the results were fully concordant with those obtained by direct DNA sequencing. ..
- Gold R, Schmied M, Rothe G, Zischler H, Breitschopf H, Wekerle H, et al. Detection of DNA fragmentation in apoptosis: application of in situ nick translation to cell culture systems and tissue sections. J Histochem Cytochem. 1993;41:1023-30 pubmed..However, this technique was not useful in detecting early stages of necrotic cell death. ..
- Nucci R, Febbraio F, Piccialli G, De Napoli L, Vaccaro C, Rossi M, et al. Interaction of the high-affinity inhibitor tetrahydro-dUMP with the allosteric enzyme deoxycytidylate aminohydrolase. Arch Biochem Biophys. 1994;310:49-53 pubmed..Such kinetics is what would be expected for a transition state analog interacting in an allosteric "K system." ..
- Barabas O, Németh V, Bodor A, Perczel A, Rosta E, Kele Z, et al. Catalytic mechanism of ?-phosphate attack in dUTPase is revealed by X-ray crystallographic snapshots of distinct intermediates, 31P-NMR spectroscopy and reaction path modelling. Nucleic Acids Res. 2013;41:10542-55 pubmed publisher..The presently used combination of diverse structural methods reveals details of the nucleophilic attack and identifies a novel enzyme-product complex structure. ..
- Sheid B. Deoxycytidylate aminohydrolase activity in the Novikoff hepatoma is dependent on the localization of the tumor. Oncology. 1990;47:278-81 pubmed
- Kümmerle E, Pomplun E. Charge build-up during decay of DNA-incorporated (123/125)I: consequences for labeled molecular structures. Int J Radiat Biol. 2012;88:922-7 pubmed publisher..The strong molecular DNA damage after (123)I and (125)I decay depends very much on the size of the DNA molecule involved in the calculation. In general, not every decay can be expected to lead to a Coulomb explosion. ..
- Chitnumsub P, Yuvaniyama J, Yavaniyama J, Vanichtanankul J, Kamchonwongpaisan S, Walkinshaw M, et al. Characterization, crystallization and preliminary X-ray analysis of bifunctional dihydrofolate reductase-thymidylate synthase from Plasmodium falciparum. Acta Crystallogr D Biol Crystallogr. 2004;60:780-3 pubmed..6 A3 Da-1). The use of a particular type of baby oil in the microbatch setup appeared to be beneficial to PfDHFR-TS crystallization and a preliminary comparison with another commonly used oil is described. ..
- Ito S, Gotoh E, Ozawa S, Yanagi K. Epstein-Barr virus nuclear antigen-1 is highly colocalized with interphase chromatin and its newly replicated regions in particular. J Gen Virol. 2002;83:2377-83 pubmed..These results suggest that EBNA-1 is associated not only with cellular metaphase chromosomes but also with condensing chromatin/chromosomes and probably with interphase chromatin, especially with its newly replicated regions. ..
- Jalabi W, Cerghet M, Skoff R, Ghandour M. Detection of oligodendrocytes in tissue sections using PCR synthesis of digoxigenin-labeled probes. J Histochem Cytochem. 2003;51:913-9 pubmed..This versatile and easy method for synthesis and labeling of specific probes to oligodendrocytes can be also applied to detect many other mRNAs in the nervous system and in other tissues. ..
- Wojcik A, von Sonntag C, Obe G. Application of the biotin-dUTP chromosome labelling technique to study the role of 5-bromo-2'-deoxyuridine in the formation of UV-induced sister chromatid exchanges in CHO cells. J Photochem Photobiol B. 2003;69:139-44 pubmed
- Edelmann P, Bornfleth H, Zink D, Cremer T, Cremer C. Morphology and dynamics of chromosome territories in living cells. Biochim Biophys Acta. 2001;1551:M29-39 pubmed..Biophys. J. 77 (1999) 2871-2886]. Here, we show that the mutual motion of different chromosome territories was independent and also 'Brownian' diffusion-like. ..
- Stout T, Stroud R. The complex of the anti-cancer therapeutic, BW1843U89, with thymidylate synthase at 2.0 A resolution: implications for a new mode of inhibition. Structure. 1996;4:67-77 pubmed..The structure suggests that this 'half-the-sites' effect is catalytic and not related to ligand binding. Therefore BW1843U89 is both a competitive inhibitor (at the binding site) and a non-competitive inhibitor at the other site. ..
- Bjornberg O, Nyman P. The dUTPases from herpes simplex virus type 1 and mouse mammary tumour virus are less specific than the Escherichia coli enzyme. J Gen Virol. 1996;77 ( Pt 12):3107-11 pubmed..The lower substrate specificity of the two virus enzymes compared with the bacterial enzyme is discussed in relation to the DNA precursor metabolism during virus replication. ..
- Aravindan G, Bjordahl J, Jost L, Evenson D. Susceptibility of human sperm to in situ DNA denaturation is strongly correlated with DNA strand breaks identified by single-cell electrophoresis. Exp Cell Res. 1997;236:231-7 pubmed
- Perevalova A, Lebedinskiĭ A, Bonch Osmolovskaia E, Chernykh N. [Detection of hyperthermophilic archaea of the genus Desulforococcus by hybridization with oligonucleotide probes]. Mikrobiologiia. 2003;72:383-9 pubmed
- Spears C, Gustavsson B. Methods for thymidylate synthase pharmacodynamics: serial biopsy, free and total TS, FdUMP and dUMP, and H4PteGlu and CH2-H4PteGlu assays. Adv Exp Med Biol. 1988;244:97-106 pubmed..H4PteGlu and CH2-H4PteGlu are measured by the Priest method using L. Casei TS. The materials and methods are described in sufficient detail to permit wide application of this approach. ..
- Sadoni N, Sullivan K, Weinzierl P, Stelzer E, Zink D. Large-scale chromatin fibers of living cells display a discontinuous functional organization. Chromosoma. 2001;110:39-51 pubmed..In particular, Cy3-labeled foci appeared as discontinuous regions of large-scale fibers. These results demonstrate that large-scale chromatin fibers have discontinuous functional characteristics. ..
- Berne M, Gustavsson B, Almersjo O, Spears C, Waldenstrom J. Concurrent allopurinol and 5-fluorouracil: 5-fluoro-2'-deoxyuridylate formation and thymidylate synthase inhibition in rat colon carcinoma and in regenerating rat liver. Cancer Chemother Pharmacol. 1987;20:193-7 pubmed..The levels of TStot increased linearly after 5-FU treatment and doubled within 48 h. In regenerating rat liver, neither FdUMP levels nor TS inhibition, studied at 1 h after bolus 5-FU, were affected by HPP pretreatment. ..
- Jackman A, Kelland L, Kimbell R, Brown M, Gibson W, Aherne G, et al. Mechanisms of acquired resistance to the quinazoline thymidylate synthase inhibitor ZD1694 (Tomudex) in one mouse and three human cell lines. Br J Cancer. 1995;71:914-24 pubmed..Cross-resistance was found to those compounds known to be active through polyglutamation. ..
- Vaughan P, McCarthy T. A novel process for mutation detection using uracil DNA-glycosylase. Nucleic Acids Res. 1998;26:810-5 pubmed..Overall, the simplicity, specificity, versatility and flexibility of the GMPD process make it an attractive candidate for both small and large scale application in mutation detection and genome analysis. ..
- Ma Y, Yang I, Tsai H, Huang C, Juo S, Wang J. High glucose modulates antiproliferative effect and cytotoxicity of 5-fluorouracil in human colon cancer cells. DNA Cell Biol. 2014;33:64-72 pubmed publisher..In conclusion, HG attenuates growth inhibition of 5-FU and our results indicate that decreased cell death and increased DNA replication may account for the attenuating effect of a HG environment on 5-FU-induced tumor growth inhibition. ..
- Ziemkowski P, Felczak K, Poznański J, Kulikowski T, Zielinski Z, Cieśla J, et al. Interactions of 2'-fluoro-substituted dUMP analogues with thymidylate synthase. Biochem Biophys Res Commun. 2007;362:37-43 pubmed..The absence of such splitting in 2',2''-diF-dUrd, indicating an unusual orientation of the base in relation to the furanose, was associated with an exceptionally weak interaction with the enzyme. ..
- Les A, Adamowicz L, Rode W. Modeling of reaction steps relevant to deoxyuridylate (dUMP) enzymatic methylation and thymidylate synthase mechanism-based inhibition. J Biomol Struct Dyn. 1998;15:703-15 pubmed..Interaction of the pyrimidine C(4)=O group, or its modification, with the N5,10-methylenetetrahydrofolate N(10) nitrogen atom is suggested as an additional factor influencing the inhibition process. ..
- Lavrik O, Kolpashchikov D, Prasad R, Sobol R, Wilson S. Binary system for selective photoaffinity labeling of base excision repair DNA polymerases. Nucleic Acids Res. 2002;30:e73 pubmed..This study illustrates use of a new method of selective labeling of DNA polymerases in a crude cellular extract. ..
- Erenpreisa J, Freivalds T, Roach H, Alston R. Apoptotic cell nuclei favour aggregation and fluorescence quenching of DNA dyes. Histochem Cell Biol. 1997;108:67-75 pubmed..In late apoptotic cells, the very dense packaging of degraded DNA promotes further aggregation of dyes. The results suggest alternative methods for detection and discrimination of early and late apoptotic cells. ..
- Finer Moore J, Fauman E, Foster P, Perry K, Santi D, Stroud R. Refined structures of substrate-bound and phosphate-bound thymidylate synthase from Lactobacillus casei. J Mol Biol. 1993;232:1101-16 pubmed..Conversion may be the result of a small change in pH in the mother liquor surrounding the crystal. A single intermolecular contact between symmetry-related Asp287 residues is disrupted on going from the small to the large crystal form. ..
- Isik F, Gibran N, Jang Y, Sandell L, Schwartz S. Vitronectin decreases microvascular endothelial cell apoptosis. J Cell Physiol. 1998;175:149-55 pubmed..Though our data confirm that vitronectin may bind to more than one integrin receptor to reduce MEC apoptosis, binding to the alpha(v) component appears to be the critical integrin subcomponent for reducing apoptosis. ..
- Majone F, Luisetto R, Zamboni D, Iwanaga Y, Jeang K. Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1) Tax target in clastogenic chromosomal instability of mammalian cells. Retrovirology. 2005;2:45 pubmed..Taken together, our findings suggest Ku80 as a cellular factor targeted by Tax in engendering clastogenic DNA damage. ..
- Dev I, Yates B, Leong J, Dallas W. Functional role of cysteine-146 in Escherichia coli thymidylate synthase. Proc Natl Acad Sci U S A. 1988;85:1472-6 pubmed..82 kcal.mol-1 (1 cal = 4.184 J) to the apparent binding energy of the substrate. ..
- Peters G, van Groeningen C, Laurensse E, Pinedo H. Thymidylate synthase from untreated human colorectal cancer and colonic mucosa: enzyme activity and inhibition by 5-fluoro-2'-deoxy-uridine-5'-monophosphate. Eur J Cancer. 1991;27:263-7 pubmed..The deviations from normal kinetics may represent a mutant TS form. Alterations in TS may partly account for differences in response to 5-FU. ..
- Wojcik A, Bruckmann E, Obe G. Insights into the mechanisms of sister chromatid exchange formation. Cytogenet Genome Res. 2004;104:304-9 pubmed..This technique was applied to study the SCEs induced by ionizing and UV radiation as well as by mitomycin C, DNaseI and AluI. This article is a review of the results and conclusions of our previous studies. ..