Topoisomerase II regulates the maintenance of DNA methylation

J Biol Chem. 2015 Jan 9;290(2):851-60. doi: 10.1074/jbc.M114.611509. Epub 2014 Dec 1.


The maintenance of DNA methylation in nascent DNA is a critical event for numerous biological processes. Following DNA replication, DNMT1 is the key enzyme that strictly copies the methylation pattern from the parental strand to the nascent DNA. However, the mechanism underlying this highly specific event is not thoroughly understood. In this study, we identified topoisomerase IIα (TopoIIα) as a novel regulator of the maintenance DNA methylation. UHRF1, a protein important for global DNA methylation, interacts with TopoIIα and regulates its localization to hemimethylated DNA. TopoIIα decatenates the hemimethylated DNA following replication, which might facilitate the methylation of the nascent strand by DNMT1. Inhibiting this activity impairs DNA methylation at multiple genomic loci. We have uncovered a novel mechanism during the maintenance of DNA methylation.

Keywords: DNA Demethylation; DNA Enzyme; DNA Methylation; DNA Methyltransferase; DNA Topoisomerase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Line
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA / metabolism
  • DNA Methylation / genetics*
  • DNA Replication / genetics
  • DNA Topoisomerases, Type II / genetics*
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Hydrolysis
  • Protein Binding / genetics
  • Ubiquitin-Protein Ligases


  • Antigens, Neoplasm
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • DNA
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases
  • DNA Topoisomerases, Type II