Search results for "NMT"

Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage/repair

2015

Reactive oxygen and nitrogen species (e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. In addition, classical regulation of gene expression or activity, including gene transcription to RNA followed by translation to the protein level, by transcription factors (e.g. NF-κB, HIF-1α) and mRNA binding proteins (e.g. GAPDH, HuR) is subject to redox regulation. This review will give an update of recent discoveries in this field, and specifically highlight the impact of reactive oxygen and nitrogen species on DNA repair systems that contribute to genomic stability. Emphasis will be placed …

DNA Methyltransferase1 post-transcriptional silencing induces aneuploidy and cell cycle arrest in human cells.

2009

The regulation of chromatin structure is a dynamic and complex process that is modulated by epigenetic mechanisms. Malfunctioning of these processes can cause gene expression alteration and could compromise important events such as chromosome condensation and segregation. Imbalance in cytosine methylation and deregulation of DNA-methyltransferases (DNMTs), and of DNMT1 in particular, is frequent in human cancers. To investigate DNMT1 implication in the generation of aneuploidy we evaluated the effects of its depletion by RNA-interference both in primary human cells (IMR90) and in near diploid human tumor (HCT116) cells. Posttranscriptional silencing of DNMT1 induced aneuploidy, cell prolife…

Bypass of G1 arrest induced by DNMT1 posttranscriptional silencing triggers aneuploidy in human cells.

2010

Aneuploidy is a major source of genomic instability in cancer, resulting from chromosome segregation errors caused by defects in genes controlling correct mitotic spindle assembly, centrosome duplication and cell cycle checkpoints. Interestingly in aneuploid cells some of these genes, although not mutated, were underexpressed suggesting the involvement of epigenetic alterations. DNA methylation and histone modifications are the main epigenetic modifications occurring in cells. DNA methyl-transferase 1 (Dnmt1) is known to restore DNA methylation patterns during cell divisions. We investigated the effects of DNMT1 silencing by RNA-interference on the generation of aneuploidy in primary human …

Methylation of cytokines gene promoters in IL-1β-treated human intestinal epithelial cells

2017

Objective and design: Epigenetic regulation is important in the activation of inflammatory cells. In the present study, we evaluated if DNA-methylation variations are involved in Interleukin-1β (IL-1β)-induced intestinal epithelial cells activation. Materials and methods: Differentiated Caco-2 cells were exposed to IL-1β or to 5-azadeoxycytidine (5-azadC) for 24 or 48 h. Genome-wide methylation status was evaluated, while DNA methylation status at the promoter region of the gene encoding interleukin-6, 8 and 10 (IL-6, 8 and 10) was estimated. The levels of the corresponding gene products as well as DNA methyltransferases (DNMTs) quantity were assessed. Results: IL-1β decreased genomic m…

The RNA methyltransferase Dnmt2 methylates DNA in the structural context of a tRNA

2016

The amino acid sequence of Dnmt2 is very similar to the catalytic domains of bacterial and eukaryotic DNA-(cytosine 5)-methyltransferases, but it efficiently catalyzes tRNA methylation, while its DNA methyltransferase activity is the subject of controversial reports with rates varying between zero and very weak. By using composite nucleic acid molecules as substrates, we surprisingly found that DNA fragments, when presented as covalent DNA-RNA hybrids in the structural context of a tRNA, can be more efficiently methylated than the corresponding natural tRNA substrate. Furthermore, by stepwise development of tRNAAsp, we showed that this natural Dnmt2 substrate could be engineered to employ R…

Targeted next generation sequencing of breast implant-associated anaplastic large cell lymphoma reveals mutations in JAK/STAT signalling pathway gene…

2016

Dzimtes stereotipu mazināšana mašīntulkošanā: mērķvalodas gramatiskās dzimtes projekcijas avotvalodā

2020

Tulkojot “The secretary asked for details.” no valodas bez gramatiskās dzimtes (angļu) uz valodu ar gramatisko dzimti (piemēram, latviešu), nepieciešams noteikt subjekta “the secretary” dzimumu. Ja teikuma līmenī nav nepieciešamās informācijas, to ne vienmēr ir iespējams izdarīt. Šādos gadījumos mašīntulkošanas sistēmas izvēlās biežāk sastopamos un līdz ar to dzimtes stereotipiem atbilstošos tulkojumu variantus (t.i. “sekretāre”). Darbā tiek piedāvāta mašīntulkošanas sistēmu apmācības metode, kur avotvalodas vārdiem ir tieši norādīta dzimtes pazīme (sieviešu vai vīriešu). Sistēmu apmācības dati tiek sagatavoti, projicējot mērķvalodas vārdu gramatiskās dzimtes uz avotvalodas vārdiem. Rezultā…

Caracterización molecular de la anemia refractaria con sideroblastos en anillo mediante un panel de secuenciación de segunda generación

2019

Los síndromes mielodisplásicos (SMD) son un grupo heterogéneo de neoplasias hematológicas que presentan citopenias, mielodisplasia, hematopoyesis ineficaz y un riesgo variable de transformación a leucemia mieloide aguda (t-LMA). Los SMD con sideroblastos en anillo (SMD-SA) constituyen aproximadamente el 10-12% de todos los SMD y en médula ósea muestran SA, eritroblastos con depósitos anormales de ferritina, en porcentaje igual o superior al 5%. El objetivo terapéutico en los SMD-SA es mejorar las citopenias y su sintomatología, en especial el síndrome anémico. La administración de eritropoyetina y el soporte transfusional con concentrados de hematíes son las opciones terpéuticas de primera …

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…

Epigenetic Mechanisms as Key Regulators in Disease

2016

Epigenetics is a rapidly growing field of research which studies the changes in the gene expression that do not involve changes in the nucleotide sequence. The cellular metabolism is directly connected to epigenetic regulation through the inflow of different metabolites such as S-adenosylmethionine, acetyl-CoA, and α-ketoglutarate among others, which serve as substrates or cofactors for chromatin-modifying enzymes. These metabolites define how our lifestyle (i.e., nutrition, physical activity, and other healthy behaviors) acts on gene expression by epigenetic mechanisms. Therefore, proper coordination between components of the epigenetic machineries is essential for the correct control of t…