6533b821fe1ef96bd127ba15
RESEARCH PRODUCT
DNA demethylation caused By 5-Aza-2'-Deoxycytidine induces mitotic alterations and aneuploidy
Viviana BarraGiuseppe CostaLaura LentiniAldo Di LeonardoDanilo Cilluffosubject
0301 basic medicineAntimetabolites Antineoplastic5-aza-2'-deoxycytidine (DAC); Aneuploidy; Chromosome methylation pattern; Chromosome Section; DNA demethylation; OncologyBlotting WesternAneuploidyMitosisApoptosisBiologymedicine.disease_causeDecitabineReal-Time Polymerase Chain ReactionChromosome Section03 medical and health scienceschromosome methylation patternChromosome instabilitymedicineTumor Cells CulturedHumansEpigeneticsaneuploidyRNA Messenger5-aza-2′-deoxycytidine (DAC)Cell ProliferationGeneticsChromosome AberrationsPloidiesReverse Transcriptase Polymerase Chain ReactionDNA Methylationmedicine.disease5-aza-2'-deoxycytidine (DAC)Gene Expression Regulation NeoplasticResearch Paper: ChromosomeSettore BIO/18 - Genetica030104 developmental biologyDNA demethylationOncologyMicroscopy FluorescenceDNA methylationColonic NeoplasmsCytogenetic AnalysisCancer researchDNA demethylationAzacitidinePloidyCarcinogenesisDNA hypomethylationdescription
Aneuploidy, the unbalanced number of chromosomes in a cell, is considered a prevalent form of genetic instability and is largely acknowledged as a condition implicated in tumorigenesis. Epigenetic alterations like DNA hypomethylation have been correlated with cancer initiation/progression. Furthermore, a growing body of evidence suggests the involvement of epigenome-wide disruption as a cause of global DNA hypomethylation in aneuploidy generation. Here, we report that the DNA hypomethylating drug 5-aza-2′-deoxycytidine (DAC), affects the correct ploidy of nearly diploid HCT-116 human cells by altering the methylation pattern of the chromosomes. Specifically, we show that a DAC-induced reduction of 5-Methyl Cytosine at the pericentromeric region of chromosomes correlates with aneuploidy and mitotic defects. Our results suggest that DNA hypomethylation leads to aneuploidy by altering the DNA methylation landscape at the centromere that is necessary to ensure proper chromosomes segregation by recruiting the proteins necessary to build up a functional kinetochore.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-01-12 |