Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination

Nucleic Acids Res. 2016 Jul 27;44(13):6242-51. doi: 10.1093/nar/gkw375. Epub 2016 Apr 30.


During DNA double-strand break and replication fork repair by homologous recombination, the RAD51 recombinase catalyzes the DNA strand exchange reaction via a helical polymer assembled on single-stranded DNA, termed the presynaptic filament. Our published work has demonstrated a dual function of the SWI5-SFR1 complex in RAD51-mediated DNA strand exchange, namely, by stabilizing the presynaptic filament and maintaining the catalytically active ATP-bound state of the filament via enhancement of ADP release. In this study, we have strived to determine the basis for physical and functional interactions between Mus musculus SWI5-SFR1 and RAD51. We found that SWI5-SFR1 preferentially associates with the oligomeric form of RAD51. Specifically, a C-terminal domain within SWI5 contributes to RAD51 interaction. With specific RAD51 interaction defective mutants of SWI5-SFR1 that we have isolated, we show that the physical interaction is indispensable for the stimulation of the recombinase activity of RAD51. Our results thus help establish the functional relevance of the trimeric RAD51-SWI5-SFR1 complex and provide insights into the mechanistic underpinnings of homology-directed DNA repair in mammalian cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • DNA Breaks, Double-Stranded
  • DNA Repair / genetics
  • DNA Replication / genetics
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Homologous Recombination / genetics*
  • Mice
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Rad51 Recombinase / chemistry*
  • Rad51 Recombinase / metabolism


  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Sfr1 protein, mouse
  • Swi5 protein, mouse
  • Adenosine Triphosphate
  • Rad51 Recombinase