Search results for "Methylation"
showing 10 items of 607 documents
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…
HPG-HMapper: A DNA hydroxymethylation analysis tool
2019
DNA methylation (mC) and hydroxymethylation (hmC) can significantly affect the normal human development, as well as health and disease status. hmC studies require not only specific treatment of DNA, but also software tools for their analysis. However, there are no software tools capable of analyzing DNA hmC currently. In this article, we propose HPG-HMapper, a parallel software tool for analyzing the DNA hmC data obtained by ten-eleven translocation–assisted bisulfite sequencing. This tool takes as input data the output files of mC aligner tools, and it yields mC maps and the accounting of methylated and hydroxymethylated bases on each chromosome. The design of this tool includes the consi…
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…
DNA integrity, growth pattern, spindle formation, chromosomal constitution and imprinting patterns of mouse oocytes from vitrified pre-antral follicl…
2010
Cryopreservation of follicles for culture and oocyte growth and maturation in vitro provides an option to increase the number of fertilizable oocytes and restore fertility in cases where transplantation of ovarian tissue poses a risk for malignant cell contamination. Vitrification for cryopreservation is fast and avoids ice crystal formation. However, the influences of exposure to high concentrations of cryoprotectants on follicle development, oocyte growth and maturation, and particularly, on the DNA integrity and methylation imprinting has not been studied systematically. Follicle survival and development, DNA damage, oocyte growth patterns, maturation, spindle formation and chromosomal c…
Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: a long road traveled and still a far way to go.
2003
Since the milestone work of Evans and Scott, demonstrating the replication dependence of alkylation-induced aberrations, and Obe and Natarajan, pointing to the critical role of DNA double-strand breaks (DSBs) as the ultimate trigger of aberrations, the field has grown extensively. A notable example is the identification of DNA methylation lesions provoking chromosome breakage (clastogenic) effects, which made it possible to model clastogenic pathways evoked by genotoxins. Experiments with repair-deficient mutants and transgenic cell lines revealed both O<sup>6</sup>-methylguanine (O<sup>6</sup>MeG) and N- methylpurines as critical lesions. For S<sub>N</sub&g…
Histone carbonylation occurs in proliferating cells
2012
12 páginas, 10 figuras (que no es encuentran en este documento, se pueden ver en: http://www.sciencedirect.com/science/article/pii/S0891584912000664)
The high rate of endoreduplication in the repair deficient CHO mutant EM9 parallels a reduced level of methylated deoxycytidine in DNA
2008
It has been recently proposed that hypomethylation of DNA induced by 5-azacytidine (5-azaC) leads to reduced chromatid decatenation that ends up in endoreduplication, most likely due to a failure in topo II function [S. Mateos, I. Domínguez, N. Pastor, G. Cantero, F. Cortés, The DNA demethylating 5-azaC induces endoreduplication in cultured Chinese hamster cells, Mutat. Res. 578 (2005) 33-42]. The Chinese hamster mutant cell line EM9 has a high spontaneous frequency of endoreduplication as compared to its parental line AA8. In order to see if this is related to the degree of DNA methylation, we have investigated the basal levels of both endpoints in AA8 and EM9, as well as the effect of ext…
Chromosomal instability, reproductive cell death and apoptosis induced by O6-methylguanine in Mex−, Mex+ and methylation-tolerant mismatch repair com…
1998
O6-Methylguanine (O6-MeG) is induced in DNA by methylating environmental carcinogens and various cytostatic drugs. It is repaired by O6-methylguanine-DNA methyltransferase (MGMT). If not repaired prior to replication, the lesion generates gene mutations and leads to cell death, sister chromatid exchanges (SCEs), chromosomal aberrations and malignant transformation. To address the question of how O6-MeG is transformed into genotoxic effects, isogenic Chinese hamster cell lines either not expressing MGMT (phenotypically Mex-), expressing MGMT (Mex+) or exhibiting the tolerance phenotype (Mex-, methylation resistant) were compared as to their clastogenic response. Mex- cells were more sensitiv…
Epigenetic control of Streptomyces coelicolor differentiation
2015
DNA cytosine methylation is one of the most important epigenetic modifications in eukaryotes regulating chromatin organization, genome maintenance and gene expression. The role of DNA cytosine methylation in prokaryotes has not been deeply investigated. In Escherichia coli cytosine methylation regulates gene expression during the stationary phase and cytosine hypermethylation leads to chromosomal DNA cleavage and cell death. Streptomyces coelicolor is a mycelial soil microorganism, which exhibits a complex life cycle that includes three different cell types: unigenomic spores, a compartmentalized mycelium (MI) and a multinucleated mycelium (substrate and aerial mycelium, MII). The importanc…
Streptomyces coelicolor: DNA methylation and differentiation
2014
DNA cytosine methylation is an epigenetic modification regulating many biological processes in eukaryotes, including chromatin organization, genome maintenance and gene expression. The role of DNA cytosine methylation in prokaryotes has not been deeply investigated. In Escherichia coli it was recently demonstrated that cytosine methylation regulates gene expression during stationary phase [1] and that an induced state of cytosine hypermethylation leads to chromosomal DNA cleavage and cell death [2]. Streptomyces coelicolor is a mycelial soil microorganism, which exhibits a complex life cycle that includes three different cell types: unigenomic spores, a compartmentalized mycelium (MI) and a…