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

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Updated: Mar 27, 2026

Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
07:50

Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina

Published on: August 29, 2018

9.6K

Giuseppe Costa1, Viviana Barra1, Laura Lentini1

  • 1Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, Italy.

Oncotarget
|January 16, 2016
PubMed

Insights

DNA hypomethylation, induced by 5-aza-2'-deoxycytidine (DAC), disrupts chromosome segregation and causes aneuploidy (abnormal chromosome numbers). This occurs by altering centromeric methylation patterns essential for kinetochore formation.

Area of Science:

  • Genetics
  • Epigenetics
  • Cell Biology

Background:

  • Aneuploidy, an abnormal chromosome number, is a hallmark of genetic instability and implicated in cancer.
  • Epigenetic changes, particularly DNA hypomethylation, are linked to cancer development and progression.
  • Evidence suggests epigenome-wide disruption contributes to DNA hypomethylation and aneuploidy.

Purpose of the Study:

  • To investigate the effect of the DNA hypomethylating drug 5-aza-2 -deoxycytidine (DAC) on chromosome ploidy.
  • To explore the relationship between DAC-induced DNA hypomethylation and aneuploidy in human cells.

Main Methods:

  • Treatment of nearly diploid HCT-116 human cells with DAC.
  • Analysis of DNA methylation patterns, specifically 5-Methyl Cytosine levels.
  • Assessment of chromosome ploidy and mitotic defects.

Main Results:

  • DAC treatment reduced 5-Methyl Cytosine levels at the pericentromeric regions of chromosomes.
  • This reduction in methylation correlated with the occurrence of aneuploidy and mitotic defects.
  • DNA hypomethylation at the centromere disrupts kinetochore assembly and proper chromosome segregation.

Conclusions:

  • DNA hypomethylation can directly lead to aneuploidy by altering centromeric epigenetic landscapes.
  • Proper chromosome segregation relies on centromeric methylation for functional kinetochore assembly.
  • Targeting DNA methylation may offer new avenues for cancer therapy by preventing aneuploidy.
Keywords:
5-aza-2’-deoxycytidine (DAC)Chromosome SectionDNA demethylationaneuploidychromosome methylation pattern

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