PIASy-dependent SUMOylation regulates DNA topoisomerase IIalpha activity

J Cell Biol. 2010 Nov 15;191(4):783-94. doi: 10.1083/jcb.201004033.


DNA topoisomerase IIα (TopoIIα) is an essential chromosome-associated enzyme with activity implicated in the resolution of tangled DNA at centromeres before anaphase onset. However, the regulatory mechanism of TopoIIα activity is not understood. Here, we show that PIASy-mediated small ubiquitin-like modifier 2/3 (SUMO2/3) modification of TopoIIα strongly inhibits TopoIIα decatenation activity. Using mass spectrometry and biochemical analysis, we demonstrate that TopoIIα is SUMOylated at lysine 660 (Lys660), a residue located in the DNA gate domain, where both DNA cleavage and religation take place. Remarkably, loss of SUMOylation on Lys660 eliminates SUMOylation-dependent inhibition of TopoIIα, which indicates that Lys660 SUMOylation is critical for PIASy-mediated inhibition of TopoIIα activity. Together, our findings provide evidence for the regulation of TopoIIα activity on mitotic chromosomes by SUMOylation. Therefore, we propose a novel mechanism for regulation of centromeric DNA catenation during mitosis by PIASy-mediated SUMOylation of TopoIIα.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • DNA Topoisomerases, Type II / genetics
  • DNA Topoisomerases, Type II / metabolism*
  • DNA, Catenated / genetics
  • DNA, Catenated / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Molecular Sequence Data
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Sumoylation
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus laevis


  • Antigens, Neoplasm
  • DNA, Catenated
  • DNA-Binding Proteins
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • Protein Inhibitors of Activated STAT
  • Recombinant Fusion Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • Xenopus Proteins
  • ran-binding protein 2
  • DNA Topoisomerases, Type II