DNA demethylation caused by 5-Aza-2’-deoxycytidine induces mitotic alterations and aneuploidy

  • Costa G
  • Barra V
  • Lentini L
  • et al.
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Abstract

// Giuseppe Costa 1,* , Viviana Barra 1,* , Laura Lentini 1 , Danilo Cilluffo 1 and Aldo Di Leonardo 1,2 1 Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, Italy 2 Centro di OncoBiologia Sperimentale (COBS), Palermo, Italy * These authors have contributed equally to this study Correspondence to: Aldo Di Leonardo, email: // Keywords : DNA demethylation, 5-aza-2’-deoxycytidine (DAC), aneuploidy, chromosome methylation pattern, Chromosome Section Received : July 20, 2015 Accepted : December 18, 2015 Published : January 12, 2016 Abstract 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.

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Costa, G., Barra, V., Lentini, L., Cilluffo, D., & Di Leonardo, A. (2016). DNA demethylation caused by 5-Aza-2’-deoxycytidine induces mitotic alterations and aneuploidy. Oncotarget, 7(4). https://doi.org/10.18632/oncotarget.6897

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