DNA Demethylation Caused by 5-Aza-2'-deoxycytidine Induces Mitotic Alterations and Aneuploidy

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jan 16

PMID 26771138

Citations 18

Authors

Giuseppe Costa

Viviana Barra

Laura Lentini

Danilo Cilluffo

Aldo Di Leonardo

Affiliations

Soon will be listed here.

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.

Citing Articles

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