Direct imaging of human Rad51 nucleoprotein dynamics on individual DNA molecules

Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):361-8. doi: 10.1073/pnas.0811965106. Epub 2009 Jan 2.

Abstract

Rad51 protein (Rad51) is central to recombinational repair of double-strand DNA breaks. It polymerizes onto DNA and promotes strand exchange between homologous chromosomes. We visualized the real-time assembly and disassembly of human Rad51 nucleoprotein filaments on double-stranded DNA by single-molecule fluorescence microscopy. Rad51 assembly extends the DNA by approximately 65%. Nucleoprotein filament formation occurs via rapid nucleation followed by growth from these nuclei. Growth does not continue indefinitely, however, and nucleoprotein filaments terminate when approximately 2 mum in length. The dependence of nascent filament formation on Rad51 concentration suggests that 2-3 Rad51 monomers are involved in nucleation. Rad51 nucleoprotein filaments are stable and remain extended when ATP hydrolysis is prevented; however, when permitted, filaments decrease in length as a result of conversion to ADP-bound nucleoprotein complexes and partial protein dissociation. Dissociation of Rad51 from dsDNA is slow and incomplete, thereby rationalizing the need for other proteins that facilitate disassembly.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / metabolism
  • DNA / metabolism*
  • Diagnostic Imaging
  • Humans
  • Intermediate Filament Proteins / metabolism
  • Kinetics
  • Microscopy, Fluorescence / methods*
  • Nucleoproteins
  • Optical Tweezers*
  • Protein Binding
  • Rad51 Recombinase / metabolism*

Substances

  • Intermediate Filament Proteins
  • Nucleoproteins
  • Adenosine Diphosphate
  • DNA
  • Rad51 Recombinase