Search results for "cytosine"

Establishment and functional validation of a structural homology model for human DNA methyltransferase 1

2003

Changes in DNA methylation patterns play an important role in tumorigenesis. The DNA methyltransferase 1 (DNMT1) protein represents a major DNA methyltransferase activity in human cells and is therefore a prominent target for experimental cancer therapies. However, there are only few available inhibitors and their high toxicity and low specificity have so far precluded their broad use in chemotherapy. Based on the strong conservation of catalytic DNA methyltransferase domains we have used a homology modeling approach to determine the three-dimensional structure of the DNMT1 catalytic domain. Our results suggest an overall structural conservation with other DNA methyltransferases but also in…

Antitumor Effects of a Combined 5-Aza-2′Deoxycytidine and Valproic Acid Treatment on Rhabdomyosarcoma and Medulloblastoma in Ptch Mutant Mice

2009

Abstract Patched (Ptch) heterozygous mice develop medulloblastoma (MB) and rhabdomyosarcoma (RMS) resembling the corresponding human tumors. We have previously shown that epigenetic silencing of the intact Ptch allele contributes to tumor formation in this model. Here, we investigated whether targeting of epigenetic silencing mechanisms could be useful in the treatment of Ptch-associated cancers. A reduction of endogenous DNA methyltransferase1 (Dnmt1) activity significantly reduced tumor incidence in heterozygous Ptch knockout mice. A combined treatment with the Dnmt inhibitor 5-aza-2′deoxycytidine (5-aza-dC) and the histone deacetlyase (HDAC) inhibitor valproic acid (VPA) efficiently prev…

Ab initio determination of the ionization potentials of DNA and RNA nucleobases

2006

Quantum chemical high level ab initio coupled-cluster and multiconfigurational perturbation methods have been used to compute vertical and adiabatic ionization potentials of the five canonical DNA and RNA nucleobases: uracil, thymine, cytosine, adenine, and guanine. Several states of their cations have been also calculated. The present results represent a systematic compendium of these magnitudes, establishing theoretical reference values at a level not reported before, calibrating computational strategies, and guiding the assignment of the features in the experimental photoelectron spectra. Daniel.Roca@uv.es Mercedes.Rubio@uv.es Manuela.Merchan@uv.es Luis.Serrano@uv.es

Deinococcus radiodurans' SRA-HNH domain containing protein Shp (Dr1533) is involved in faithful genome inheritance maintenance following DNA damage

2018

WOS:000452343100012; International audience; Background: Deinococcus radiodurans R1 (DR) survives conditions of extreme desiccation, irradiation and exposure to genotoxic chemicals, due to efficient DNA breaks repair, also through Mn2+ protection of DNA repair enzymes. Methods: Possible annotated domains of the DR1533 locus protein (Shp) were searched by bioinformatic analysis. The gene was cloned and expressed as fusion protein. Band-shift assays of Shp or the SRA and HNH domains were performed on oligonucleotides, genomic DNA from E. coif and DR. slip knock-out mutant was generated by homologous recombination with a kanamycin resistance cassette. Results: DR1533 contains an N-terminal SRA…

The DNA cytosine methylome of Streptomyces coelicolor

2019

Experimental and theoretical studies on thymine photodimerization mediated by oxidatively generated DNA lesions and epigenetic intermediates.

2020

[EN] Interaction of nucleic acids with light is a scientific question of paramount relevance not only in the understanding of life functioning and evolution, but also in the insurgence of diseases such as malignant skin cancer and in the development of biomarkers and novel light-assisted therapeutic tools. This work shows that the UVA portion of sunlight, not absorbed by canonical DNA nucleobases, can be absorbed by 5-formyluracil (ForU) and 5-formylcytosine (ForC), two ubiquitous oxidatively generated lesions and epigenetic intermediates present in living beings in natural conditions. We measure the strong propensity of these molecules to populate triplet excited states able to transfer th…

The effect of arabinofuranosyl-cytosine upon the synthesis of herpesvirus hominis Electron microscopic observations in relation to viral DNA-synthesis

1972

The paper describes experiments about the degree of dependency of capsid, envelope and antigen synthesis byherpesvirus hominis upon viral DNA synthesis. The DNA synthesis has been blocked by different doses of Ara-C and the remnant DNA-synthesis has been measured by [3H]-thymidine incorporation after CsCl-density gradient centrifugation. Electron microscopic studies were done in parallel after incubation of infected cells with different doses of Ara-C. Finally, antigens were prepared after infection without and with added Ara-C. Increasing amounts of Ara-C inhibited the synthesis of viral DNA and infective particles. 1.5 μg Ara-C reduced the remaining incorporation into DNA to about less th…

Comprehensive DNA methylation analysis of the Aedes aegypti genome

2016

AbstractAedes aegypti mosquitoes are important vectors of viral diseases. Mosquito host factors play key roles in virus control and it has been suggested that dengue virus replication is regulated by Dnmt2-mediated DNA methylation. However, recent studies have shown that Dnmt2 is a tRNA methyltransferase and that Dnmt2-dependent methylomes lack defined DNA methylation patterns, thus necessitating a systematic re-evaluation of the mosquito genome methylation status. We have now searched the Ae. aegypti genome for candidate DNA modification enzymes. This failed to reveal any known (cytosine-5) DNA methyltransferases, but identified homologues for the Dnmt2 tRNA methyltransferase, the Mettl4 (…

The Rate and Molecular Spectrum of Spontaneous Mutations in Arabidopsis thaliana

2010

Evolution in Action Rates of evolution in gene and genome sequences have been estimated, but these estimates are subject to error because many of the steps of evolution over the ages are not directly measurable or are hidden under subsequent changes. Ossowski et al. (p. 92 ) now provide a more accurate measurement of how often spontaneous mutations arise in a nuclear genome. Mutations arising over 30 generations were compared by sequencing DNA from individual Arabidopsis thaliana plants. UV- and deamination-induced mutagenesis appeared to bias the type of mutations found.

Zwitterionic Sulfonates as m/z Shift Reagents for 5-Methylcytosine Detection in Deoxyribonucleic Acids (DNA) Using Flow Injection Analysis and Electr…

2015

5-Methylcytosine (5-MC) is an important epigenetic modification of DNA. Abnormally high concentrations of this substance appear because of the hypermethylation of cytosine. Therefore, the measurement of the quantity of this compound in mammals is of great importance. Recently, we reported that several imidazolium-based zwitterionic sulfonates form complexes with 5-MC in solution, which can be studied by electrospray ionisation mass spectrometry (ESI-MS). It is shown in this paper that such an association can be utilised for the detection of 5-MC in a DNA sample using high-throughput a flow injection analysis ESI-MS method. A variety of the sulfonate zwitterions have been tested as m/ z shi…