Visualization of the annealing of complementary single-stranded DNA catalyzed by the herpes simplex virus type 1 ICP8 SSB/recombinase

J Mol Biol. 2006 Feb 3;355(5):911-22. doi: 10.1016/j.jmb.2005.11.022. Epub 2005 Nov 28.

Abstract

The rate of annealing of long linear complementary single-stranded (ss) DNAs can be increased greatly by certain DNA-binding proteins including the herpes simplex virus type 1 ICP8 SSB/recombinase. Using electron microscopy, we have investigated the DNA-protein structures involved in ICP8-mediated DNA annealing. We show that the formation of superhelical ICP8-ssDNA filaments is required for annealing. Two superhelices interact with each other to form a coiled-coil, which is the intermediate in annealing. In this process, the superhelices likely rotate and translocate relative to each other. Psoralen/UV photocrosslinking studies revealed that meta-stable contacts form at sites of limited sequence homology during the annealing. Partial proteolysis of ICP8 in the protein-ssDNA complexes showed that Mg2+ induces conformational changes in the N-terminal region (amino acid residues 1-305) of ICP8. In addition to Mg2+, Ca2+ and, to a significantly lesser extent, Cu2+ and Mn2+, were found to induce superhelix formation of the ICP8-ssDNA filament and to facilitate annealing. Mechanisms for how the coiled-coil structures facilitate annealing are discussed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cross-Linking Reagents / metabolism
  • DNA, Single-Stranded* / chemistry
  • DNA, Single-Stranded* / metabolism
  • DNA, Single-Stranded* / ultrastructure
  • DNA-Binding Proteins
  • Ficusin / metabolism
  • Magnesium / metabolism
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Protein Conformation*
  • Protein Renaturation
  • Recombinases / metabolism*
  • Recombinases / ultrastructure
  • Viral Proteins / metabolism*
  • Viral Proteins / ultrastructure

Substances

  • Cross-Linking Reagents
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • ICP8 protein, Simplexvirus
  • Recombinases
  • Viral Proteins
  • Magnesium
  • Ficusin