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Bioorganic & Medicinal Chemistry Jan 20135-Bromouracil ((Br)U) was incorporated into three types of synthetic RNA and the products of the photoirradiated (Br)U-containing RNAs were investigated using HPLC and...
5-Bromouracil ((Br)U) was incorporated into three types of synthetic RNA and the products of the photoirradiated (Br)U-containing RNAs were investigated using HPLC and MS analysis. The photoirradiation of r(GCA(Br)UGC)(2) and r(CGAA(Br)UUGC)/r(GCAAUUCG) in A-form RNA produced the corresponding 2'-keto adenosine ((keto)A) product at the 5'-neighboring nucleotide, such as r(GC(keto)AUGC) and r(CGA(keto)AUUGC), respectively. The photoirradiation of r(CGCG(Br)UGCG)/r(C(m)GCAC(m)GCG) in Z-form RNA produced the 2'-keto guanosine ((keto)G) product r(CGC(keto)GUGCG), whereas almost no products were observed from the photoirradiation of r(CGCG(Br)UGCG)/r(C(m)GCAC(m)GCG) in A-form RNA. The present results indicate clearly that hydrogen (H) abstraction by the photochemically generated uracil-5-yl radical selectively occurs at the C2' position to provide a 2'-keto RNA product.
Topics: Bromouracil; Chromatography, High Pressure Liquid; Light; RNA; Spectrometry, Mass, Electrospray Ionization
PubMed: 23266180
DOI: 10.1016/j.bmc.2012.11.010 -
Cell Dec 2008Bone marrow hematopoietic stem cells (HSCs) are crucial to maintain lifelong production of all blood cells. Although HSCs divide infrequently, it is thought that the...
Bone marrow hematopoietic stem cells (HSCs) are crucial to maintain lifelong production of all blood cells. Although HSCs divide infrequently, it is thought that the entire HSC pool turns over every few weeks, suggesting that HSCs regularly enter and exit cell cycle. Here, we combine flow cytometry with label-retaining assays (BrdU and histone H2B-GFP) to identify a population of dormant mouse HSCs (d-HSCs) within the lin(-)Sca1+cKit+CD150+CD48(-)CD34(-) population. Computational modeling suggests that d-HSCs divide about every 145 days, or five times per lifetime. d-HSCs harbor the vast majority of multilineage long-term self-renewal activity. While they form a silent reservoir of the most potent HSCs during homeostasis, they are efficiently activated to self-renew in response to bone marrow injury or G-CSF stimulation. After re-establishment of homeostasis, activated HSCs return to dormancy, suggesting that HSCs are not stochastically entering the cell cycle but reversibly switch from dormancy to self-renewal under conditions of hematopoietic stress.
Topics: Adult Stem Cells; Animals; Antigens, Differentiation; Bone Marrow; Bromouracil; Fluorouracil; Green Fluorescent Proteins; Hematopoietic Stem Cells; Homeostasis; Mice; Mice, Transgenic; Uridine
PubMed: 19062086
DOI: 10.1016/j.cell.2008.10.048 -
Quarterly Reviews of Biophysics May 1973
Review
Topics: Bromouracil; DNA; DNA Repair; DNA, Single-Stranded; Free Radicals; Photochemistry; Pyrimidines; Radiation Effects; Spectrophotometry, Ultraviolet; Ultraviolet Rays; Uracil
PubMed: 4579676
DOI: 10.1017/s0033583500001141 -
Mutation Research Oct 1978A screening procedure based on the formation of papillae on individual bacterial colonies was used to isolate mutants of Escherichia coli with high mutation rates in the...
A screening procedure based on the formation of papillae on individual bacterial colonies was used to isolate mutants of Escherichia coli with high mutation rates in the presence of bromouracil. Most of the mutants obtained had high spontaneous mutation rates and mapped close to the previously known mutators mutT, mutS, mutR, uvrE and mutL. Except for mutants of mutT type, these mutators also showed high mutability by bromouracil. Transfection experiments were performed with heteroduplex lambda DNA to test for mismatch repair. The results suggest a reduced efficiency of repair of mismatched bases in mutators mutS, mutR, uvrE and mutL, whereas mutants mapping as mutT appear normal. The results support a connection between spontaneous and bromouracil-induced mutability and repair of mismatched bases in DNA.
Topics: Bromouracil; Coliphages; DNA Repair; Escherichia coli; Mutagens; Mutation; Transfection
PubMed: 366396
DOI: 10.1016/0027-5107(78)90091-x -
Molecular & General Genetics : MGG Mar 1977
Topics: Amino Acids; Bromouracil; DNA Repair; DNA, Bacterial; Dose-Response Relationship, Drug; Escherichia coli
PubMed: 325383
DOI: 10.1007/BF00264935 -
Photochemistry and Photobiology May 20225-Halouracil, which is a DNA base analog in which the methyl group at the C5 position of thymine is replaced with a halogen atom, has been used in studies of DNA damage.... (Review)
Review
5-Halouracil, which is a DNA base analog in which the methyl group at the C5 position of thymine is replaced with a halogen atom, has been used in studies of DNA damage. In DNA strands, the uracil radical generated from 5-halouracil causes DNA damage via a hydrogen-abstraction reaction. We analyzed the photoreaction of 5-halouracil in various DNA structures and revealed that the reaction is DNA structure-dependent. In this review, we summarize the results of the analysis of the reactivity of 5-halouracil in various DNA local structures. Among the 5-halouracil molecules, 5-bromouracil has been used as a probe in the analysis of photoinduced electron transfer through DNA. The analysis of groove-binder/DNA and protein/DNA complexes using a 5-bromouracil-based electron transfer system is also described.
Topics: Bromouracil; DNA; Thymine; Uracil
PubMed: 34543451
DOI: 10.1111/php.13521 -
Zeitschrift Fur Allgemeine Mikrobiologie 1983The presence of 5-bromouracil (BU) as well as 5-bromo-2-deoxyuridine (BUdR) in the cultivation media of bacteria results in the distinct increase of UV sensitivity. With... (Review)
Review
The presence of 5-bromouracil (BU) as well as 5-bromo-2-deoxyuridine (BUdR) in the cultivation media of bacteria results in the distinct increase of UV sensitivity. With the nucleic acid base analogue 8-azaadenine (8-AA) a similar effect was confirmed, however, not so pronounced. In the experiments reported here the combined action of BU or BUdR and 8-AA on Escherichia coli, Proteus mirabilis, Bacillus subtilis and Bacillus cereus was investigated. The sensitization effect of BUdR does not increase if 8-AA is present additionally during cultivation. On the contrary, a decrease of sensibilization occurs. This result may be caused by the protective effect of the adenine derivative against UV irradiation, if it is present in the cell, but not incorporated into the DNA.
Topics: Adenine; Bacillus cereus; Bacillus subtilis; Bacteria; Bromodeoxyuridine; Bromouracil; Escherichia coli; Proteus mirabilis; Radiation Tolerance; Radiation-Sensitizing Agents; Ultraviolet Rays
PubMed: 6419483
DOI: 10.1002/jobm.3630230807 -
Photochemical & Photobiological... Jan 2011The photoreactions of 5-bromouracil (BrUra) induced by 254 nm radiation have received a significant amount of scrutiny over the years, both when induced in liquid...
The photoreactions of 5-bromouracil (BrUra) induced by 254 nm radiation have received a significant amount of scrutiny over the years, both when induced in liquid aqueous solution and in the frozen state. The characterized photoproducts in the liquid state include uracil, 5,5'-diuracil (I) and a variety of products arising from ring opening, while the photoreactivity of BrUra in ice using 254 nm radiation is very low. During examination of the photoreactions induced in BrUra in frozen aqueous solution by exposure to predominately UVB irradiation, we found that several products are formed. One of these products has an ultraviolet absorption spectrum similar to those associated with (6-4) adducts of the pyrimidine bases (λ(max) = 326 nm). Studies with (1)H and (13)C nuclear magnetic resonance spectroscopy and with mass spectrometry yielded data consistent with this compound indeed being a (6-4) product, namely 6-4'-(5'-bromopyrimidin-2'-one)-5,5-dihydroxy-5,6-dihydrouracil (IIa). The product IIa probably arises from an unstable precursor, namely 5-bromo-6-4'-(5'-bromopyrimidin-2'-one)-5-hydroxy-5,6-dihydrouracil (IV); this compound is a bromohydrin and, as such, is likely unstable to debromination to 6-4'-(5'-bromopyrimidin-2'-one)-5-oxo-5,6-dihydrouracil (V). Rehydration at the 5-position to form a gem diol would lead to IIa, the isolated product.
Topics: Bromouracil; DNA Adducts; Ice; Mass Spectrometry; Pyrimidinones; Solutions; Ultraviolet Rays; Uracil
PubMed: 20976373
DOI: 10.1039/c0pp00242a -
Philosophical Transactions. Series A,... Apr 20175-Bromouracil is a nucleobase analogue that can replace thymine in DNA strands and acts as a strong radiosensitizer, with potential applications in molecular biology and...
5-Bromouracil is a nucleobase analogue that can replace thymine in DNA strands and acts as a strong radiosensitizer, with potential applications in molecular biology and cancer therapy. Here, the deactivation of 5-bromouracil after ultraviolet irradiation is investigated in the singlet and triplet manifold by accurate quantum chemistry calculations and non-adiabatic dynamics simulations. It is found that, after irradiation to the bright * state, three main relaxation pathways are, in principle, possible: relaxation back to the ground state, intersystem crossing (ISC) and C-Br photodissociation. Based on accurate MS-CASPT2 optimizations, we propose that ground-state relaxation should be the predominant deactivation pathway in the gas phase. We then employ different electronic structure methods to assess their suitability to carry out excited-state dynamics simulations. MRCIS (multi-reference configuration interaction including single excitations) was used in surface hopping simulations to compute the ultrafast ISC dynamics, which mostly involves the * and * states.This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.
Topics: Absorption, Physicochemical; Bromouracil; Electrons; Models, Molecular; Molecular Conformation; Quantum Theory; Ultraviolet Rays
PubMed: 28320905
DOI: 10.1098/rsta.2016.0202 -
Journal of Bacteriology Nov 19725-Bromouracil (BU)-tolerant mutants of Bacillus subtilis 23 (thy his) have been isolated. Several classes of tolerant mutants were obtained by a sequential selection...
5-Bromouracil (BU)-tolerant mutants of Bacillus subtilis 23 (thy his) have been isolated. Several classes of tolerant mutants were obtained by a sequential selection procedure. The classes can be distinguished by their relative BU tolerance as well as several other phenotypic characteristics. The mutants can grow for an extended period of time in minimal medium supplemented with amino acids and BU, in which the sensitive parental strain (Bu(+)) undergoes rapid cell death. Both mutants But-1 and But-1310 have a greater rate of deoxyribonucleic acid (DNA) synthesis by a factor of two in the presence of BU than Bu(+), But-1 being somewhat faster than But-1310. The preferential incorporation of thymine to BU of But-1 is about half that of the Bu(+) strain during DNA replication in minimal medium supplemented with 10 mug of BU/ml and 1 mug of thymine/ml. It is not known at what step or steps this reduction in selectivity occurs.
Topics: Bacillus subtilis; Bromouracil; Caffeine; Carbon Isotopes; Cell Survival; Chromosome Mapping; Culture Media; DNA Replication; DNA, Bacterial; Drug Resistance, Microbial; Mutation; Radiation Effects; Spores, Bacterial; Thymine; Transformation, Genetic; Ultraviolet Rays; Uracil
PubMed: 4628747
DOI: 10.1128/jb.112.2.870-876.1972