Search results for "DNMT"

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…

DNMT1 transient silencing induces aneuploidy, premature separated chromatids and centromeric chromatin alterations

2008

DNMT1 SILENCING ELICITS DIFFERENT CELL CYCLE RESPONSES IN PRIMARY VERSUS TUMOR CELLS AND IS ASSOCIATED WITH ANEUPLOIDY GENERATION

2011

DNMT1 depletion activates a pathway p14ARF/TP53 controlled that induces G1 arrest preventing DNA demethylation and aneuploidy

2011

Background: Aneuploidy is considered the result of chromosome segregation errors caused by defects in the mitotic spindle assembly, centrosome duplication, cell-cycle checkpoints and epigenetic changes. Usually, aneuploidy affects negatively proliferation of normal cells. However, it is frequently associated with cancer that is characterized by a uncontrolled proliferation. Thus, understanding the pathway(s) that block proliferation of aneuploid cells might open new avenue to exploit new cancer therapies. O bservations: We found that in primary human fi broblasts (IMR90) knocking down of DNMT1, a member of epigenetic machinery is perceived by the cell as a stress signal that induces p14ARF …

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 …

Cytosine methylation of tRNA-Asp by DNMT2 has a role in translation of proteins containing poly-Asp sequences

2015

AbstractThe Dnmt2 RNA methyltransferase catalyses the methylation of C38 in the anticodon loop of tRNA-Asp, but the molecular role of this methylation is unknown. Here, we report that mouse aspartyl-tRNA synthetase shows a four to fivefold preference for C38-methylated tRNA-Asp. Consistently, a 30% reduced charging level of tRNA-Asp was observed in Dnmt2 knockout (KO) murine embryonic fibroblast cells. Gene expression analysis with fluorescent reporter proteins fused to an N-terminal poly-Asp sequence showed that protein synthesis of poly-Asp-tagged reporter proteins was reduced in Dnmt2 KO cells as well. The same effect was observed with endogenous proteins containing poly-Asp sequences, i…

MiR-221 promotes stemness of breast cancer cells by targeting DNMT3b

2016

// Giuseppina Roscigno 1, 2 , Cristina Quintavalle 1, 2 , Elvira Donnarumma 3 , Ilaria Puoti 1 , Angel Diaz-Lagares 4 , Margherita Iaboni 1 , Danilo Fiore 1 , Valentina Russo 1 , Matilde Todaro 5 , Giulia Romano 6 , Renato Thomas 7 , Giuseppina Cortino 7 , Miriam Gaggianesi 5 , Manel Esteller 4 , Carlo M. Croce 6 , Gerolama Condorelli 1, 2 1 Department of Molecular Medicine and Medical Biotechnology, “Federico II” University of Naples, Naples, Italy 2 IEOS-CNR, Naples, Italy 3 IRCCS-SDN, Naples, Italy 4 Epigenetic and Cancer Biology Program (PEBC) IDIBELL, Hospital Duran I Reynals, Barcelona, Spain 5 Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Lab…

Effects of 5-Azacitidine on Dnmt2/Trdmt1 expression levels and endoplasmic reticulum stress in cellular models of insulinoma

2021

Diabetes mellitus affects people all over the world of all ages or social groups making it a worldwide healthcare challenge. Moreover, untreated or badly treated diabetes carries a risk of serious complications including premature death (IDF Diabetes Atlas 9th edition, 2019). The main symptom of diabetes is insulin secretion and/or action disorder leading to hyperglycemia what results in impaired carbohydrate, fat, and protein metabolism (“Diagnosis and Classification of Diabetes Mellitus,” 2013). Dnmt2/ Trdmt1 in its structure and sequence is similar to DNA methyltransferases, however, it has been shown that mainly methylates aspartic acid transfer RNA, specifically at the cytosine-38 resi…