Search results for "Telomere"
showing 10 items of 153 documents
Telomerase activity and telomeric states in cell proliferative and differentiative mechanisms.
2008
Telomeres are DNA-protein complexes playing an important role in the maintenance of genome integrity. Telomerase is the enzyme acting as a template for addition of new telomeric repeats; this addition is essential for those cellular populations that have proliferative and differentiative potential. Telomerase and associated proteins are essential in response to DNA damage. Moreover, telomere-associated proteins as TRF2 are involved in all signalling transduction pathway which drive cellular proliferation and differentiation. In somatic cells, shortening of telomeres contributes to the onset of senescence or apoptosis; tissues which require cellular renewal express telomerase activity in ord…
Telomere dysfunction in cells with arsenic-induced genomic instability
2005
It is well known that the occurrence of dicentric chromosomes represent signature of telomere dysfunction and is a clear symptom of genomic instability. V79 Chinese hamster cells, treated with 10µM sodium arsenite for 24h and allowed to grow in drug-free medium (ASO cells), showed genomic instability with aneuploidy and nuclear abnormalities as well as the appearance of dicentric chromosomes since the 90th cell generation. TRAP assay was performed on growing ASO cells and on clones isolated during the course of the expanded growth. As expected, some clones with dicentric chromosomes and severely reduced telomerase activity went to death; surprisingly, other clones also bearing chromosomal e…
From cellular senescence to age-associated diseases: miRNAs as tools and targets for healthy ageing
2017
miRNAs are the most abundant RNA species to be found in cell-free blood, encapsulated within microvesicles or bound to proteins. miRNAs play essential roles in the regulation of various biological processes. Moreover, specific changes in miRNA transcription levels or miRNA secretory levels have been linked to the development and progression of certain age-related diseases. So, they might be an ideal target for modulating healthy ageing
Molecular recognition of naphthalene diimide ligands by telomeric quadruplex-DNA: the importance of the protonation state and mediated hydrogen bonds.
2016
In depth Monte Carlo conformational scans in combination with molecular dynamics (MD) simulations and electronic structure calculations were applied in order to study the molecular recognition process between tetrasubstituted naphthalene diimide (ND) guests and G-quadruplex (G4) DNA receptors. ND guests are a promising class of telomere stabilizers due to which they are used in novel anticancer therapeutics. Though several ND guests have been studied experimentally in the past, the protonation state under physiological conditions is still unclear. Based on chemical intuition, in the case of N-methyl-piperazine substitution, different protonation states are possible and might play a crucial …
Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action
2015
Abstract Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2′-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progressi…
Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells.
2004
Chromosome integrity is essential for cell viability and, therefore, highly proliferative cell types require active telomere elongation mechanisms to grow indefinitely. Consistently, deletion of telomerase activity in a genetically modified mouse strain results in growth impairments in all highly proliferative cell populations analyzed so far. We show that telomere attrition dramatically impairs the in vitro proliferation of adult neural stem cells (NSCs) isolated from the subventricular zone (SVZ) of telomerase-deficient adult mice. Reduced proliferation of postnatal neurogenic progenitors was also observed in vivo, in the absence of exogenous mitogenic stimulation. Strikingly, severe telo…
Expression of the genetic suppressor element 24.2 (GSE24.2) decreases DNA damage and oxidative stress in X-linked dyskeratosis congenita cells.
2014
This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Deciphering the DNAzyme activity of multimeric quadruplexes: insights into their actual role in the telomerase activity evaluation assay.
2011
The end of human telomeres is comprised of a long G-rich single-stranded DNA (known as 3'-overhang) able to adopt an unusual three-dimensional "beads-on-the-string" organization made of consecutively stacked G-quadruplex units (so-called quadruplex multimers). It has been widely demonstrated that, upon interaction with hemin, discrete quadruplexes acquire peroxidase-mimicking properties, oxidizing several organic probes in H(2)O(2)-rich conditions; this property, known as DNAzyme, has found tens of applications in the last two decades. However, little is known about the DNAzyme activity of multimeric quadruplexes; this is an important question to address, especially in light of recent repor…
snoRNPs Regulate Telomerase Activity in Neuroblastoma and Are Associated with Poor Prognosis
2013
AbstractAmplification of the MYCN oncogene is strongly associated with poor prognosis in neuroblastoma (NB). In addition to MYCN amplification, many studies have focused on identifying patients with a poor prognosis based on gene expression profiling. The majority of prognostic signatures today are comprised of large gene lists limiting their clinical application. In addition, although of prognostic significance,most of these signatures fail to identify cellular processes that can explain their relation to prognosis. Here, we determined prognostically predictive genes in a data set containing 251 NBs. Gene Ontology analysis was performed on significant genes with a positive hazard ratio to …
Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer
2013
Journal article TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10!-7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10!-8) and BRCA1 mutation carrier (P = 1.1 × 10!-5) breast cancers and altered promot…