Search results for " genetica"

Genetic discontinuities within the Mediterranean basin. Post-glacial recolonization patterns and recent current regime

2009

Functional antagonism between histone H3K4 demethylases in vivo

2011

Dynamic regulation of histone modifications is critical during development, and aberrant activity of chromatin-modifying enzymes has been associated with diseases such as cancer. Histone demethylases have been shown to play a key role in eukaryotic gene transcription; however, little is known about how their activities are coordinated in vivo to regulate specific biological processes. In Drosophila, two enzymes, dLsd1 (Drosophila ortholog of lysine-specific demethylase 1) and Lid (little imaginal discs), demethylate histone H3 at Lys 4 (H3K4), a residue whose methylation is associated with actively transcribed genes. Our studies show that compound mutation of Lid and dLsd1 results in increa…

LA GENETICA GENERALE

2013

Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells

2017

Optimization of a new lead promoting the readthrough of the nonsense mutations for CFTR rescue in human CF cells Laura Lentini, Raffaella Melfi, Sara Baldassano, Marco Tutone, Aldo Di Leonardo, Andrea Pace, Ivana Pibiri Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo Background and rationale Cystic Fibrosis patients with nonsense mutations in the CFTR gene have a more severe form of the disease. Nonsense mutations represent about 10% of the mutations that affect the CFTR gene and they are frequently associated to the classical F508 mutation (1). A potential treatment for this genetic alteration is to promote the translationa…

Biochemical approaches to characterize targets responsible for acrylamide-induced inhibition of topoisomerase II

2006

Vinyl monomer acrylamide (AA), generally used in numerous industrial applications, has been classified by the International Agency for Research on Cancer (IARC) as “probably carcinogenic to humans” (group 2A), but the molecular mechanism underlying its genotoxicity has not fully known. Previously, we observed that Acrylamide (AA) was able to antagonize in vivo the citotoxicity of well know poison etoposide suggesting that topoisomerase II (Topo II) activity was affected by AA. In the current studies we investigated the inhibitory activity of acrylamide toward topoisomerase II by performing tests in vitro.

In vivo and in vitro inhibitory effects of acrylamide on DNA topoisomerase II

2006

Acrylamide (AA), a chemical produced in several foodstuffs when cooked at a high temperature, is considered a probable human carcinogen, but the molecular mechanism underlying its genotoxicity has not fully known. Numerous authors have reported the induction by AA of DNA double strand breaks and sister chromatid exchange (SCE); we here confirmed the acrylamide capability of damaging DNA by utilizing Comet assay, which showed a dose-dependent increase of tail lenght, in metabolically non competent V79 Chinese hamster cells. Moreover, we observed that Acrylamide (AA) was able to antagonize in vivo the citotoxicity of well know poison etoposide; this suggested that topoisomerase II activity wa…

UPREGULATION OF MIR-29A AND GENOMIC DNA HYPERMETHYLATION IN NORMAL KARYOTYPE AML SHOWING DNMT3A MUTATION UPREGOLAZIONE DEL MIR-29A E IPERMETILAZIONE …

2015

DNMT3A, a member of DNA methyltransferases, is mutated in approximately 22% of de novo normal karyotype acute myeloid leukemia (NK-AML) patients leading to adverse overall survival. The highly recurrent mutation in DNMT3A is a “gain of function-like” at codon R882. To indagate about miRNA signature in NK-AML R882-DNMT3A mutated we studied by qRT-PCR the expression of 384 known human miRNA in 9 selected de-novo AML DNMT3A mutated. We compared miRNA expression data with our previous results obtained in 31 AML DNMT3A wild type (WT) and we focused on a strong up-regulation of miR155, miR29a, miR196b and miR25. We consolidated this data in additional 24 new DNMT3A mutated AML and we confirmed th…

The tumor suppressor p14ARF hampers proliferation of aneuploid cells induced by CENP-E partial depletion

The Spindle Assembly Checkpoint (SAC) is a cellular surveillance mechanism that ensures faithfully segregation of chromosomes. Reduced expression of some of its components weakens the SAC and induces chromosome instability and aneuploidy, both hallmarks of tumor cells. Centromere Protein-E (CENP-E) is a crucial component of the SAC and facilitates kinetochore microtubule attachment required to achieve and maintain chromosome alignment. To investigate the possible role of p14ARF on aneuploid cells proliferation we induced aneuploidy in primary human fibroblasts (IMR90) and in near diploid tumor cells (HCT116) by partial depletion of CENP-E obtained by RNA interference. Our results show that …

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 …

Identification of pathways involved in aneuploidy onset and its tolerance using a DNA microarray approach

2013

Genomic instability is a hallmark of the majority of human tumors explaining the heterogeneity shown by tumor cells. This phenomenon is often associated with chromosomal instability (CIN) and aneuploidy, a condition in which tumor cells lose or gain chromosomes. Previously, we showed that posttranscriptional silencing by RNAi of pRb1, DNMT12 and MAD2 is associated with aneuploidy in cultured human cells reinforcing the idea that there are several roads leading to aneuploidy. In the attempt to understand if a common molecular signature exists underlying aneuploidy and its tolerance in tumor cells, we induced aneuploidy in human fibroblasts (IMR90) by depleting Rb, MAD2 and DNMT1 genes and an…