All tangled up: how cells direct, manage and exploit topoisomerase function

Nat Rev Mol Cell Biol. 2011 Nov 23;12(12):827-41. doi: 10.1038/nrm3228.


Topoisomerases are complex molecular machines that modulate DNA topology to maintain chromosome superstructure and integrity. Although capable of stand-alone activity in vitro, topoisomerases are frequently linked to larger pathways and systems that resolve specific DNA superstructures and intermediates arising from cellular processes such as DNA repair, transcription, replication and chromosome compaction. Topoisomerase activity is indispensible to cells, but requires the transient breakage of DNA strands. This property has been exploited, often for significant clinical benefit, by various exogenous agents that interfere with cell proliferation. Despite decades of study, surprising findings involving topoisomerases continue to emerge with respect to their cellular function, regulation and utility as therapeutic targets.

Publication types

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

MeSH terms

  • Animals
  • Chromosome Segregation
  • DNA / chemistry
  • DNA / metabolism
  • DNA Replication
  • DNA Topoisomerases / chemistry
  • DNA Topoisomerases / metabolism*
  • Gene Expression Regulation
  • Humans
  • Topoisomerase Inhibitors / therapeutic use


  • Topoisomerase Inhibitors
  • DNA
  • DNA Topoisomerases