Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism

Mol Cell. 2015 Feb 19;57(4):595-606. doi: 10.1016/j.molcel.2015.01.022.


The displacement loop (D loop) is a DNA strand invasion product formed during homologous recombination. Disruption of nascent D loops prevents recombination, and during synthesis-dependent strand annealing (SDSA), disruption of D loops extended by DNA polymerase ensures a non-crossover outcome. The proteins implicated in D loop disruption are DNA motor proteins/helicases that act by moving DNA junctions. Here we report that D loops can also be disrupted by DNA topoisomerase 3 (Top3), and this disruption depends on Top3's catalytic activity. Yeast Top3 specifically disrupts D loops mediated by yeast Rad51/Rad54; protein-free D loops or D loop mediated by bacterial RecA protein or human RAD51/RAD54 resist dissolution. Also, the human Topoisomerase IIIa-RMI1-RMI2 complex is capable of dissolving D loops. Consistent with genetic data, we suggest that the extreme growth defect and hyper-recombination phenotype of Top3-deficient yeast cells is partially a result of unprocessed D loops.

Publication types

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

MeSH terms

  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Helicases / physiology
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • DNA Repair Enzymes / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Homologous Recombination / physiology*
  • Humans
  • Models, Genetic*
  • Rad51 Recombinase / metabolism
  • Rad51 Recombinase / physiology*
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism
  • RecQ Helicases / physiology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Species Specificity


  • DNA-Binding Proteins
  • Rmi1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • TOP3 protein, S cerevisiae
  • RAD51 protein, S cerevisiae
  • Rad51 Recombinase
  • RAD54 protein, S cerevisiae
  • SGS1 protein, S cerevisiae
  • DNA Helicases
  • RecQ Helicases
  • DNA Repair Enzymes