A dynamic model for replication protein A (RPA) function in DNA processing pathways

Nucleic Acids Res. 2006;34(15):4126-37. doi: 10.1093/nar/gkl550. Epub 2006 Aug 25.


Processing of DNA in replication, repair and recombination pathways in cells of all organisms requires the participation of at least one major single-stranded DNA (ssDNA)-binding protein. This protein protects ssDNA from nucleolytic damage, prevents hairpin formation and blocks DNA reannealing until the processing pathway is successfully completed. Many ssDNA-binding proteins interact physically and functionally with a variety of other DNA processing proteins. These interactions are thought to temporally order and guide the parade of proteins that 'trade places' on the ssDNA, a model known as 'hand-off', as the processing pathway progresses. How this hand-off mechanism works remains poorly understood. Recent studies of the conserved eukaryotic ssDNA-binding protein replication protein A (RPA) suggest a novel mechanism by which proteins may trade places on ssDNA by binding to RPA and mediating conformation changes that alter the ssDNA-binding properties of RPA. This article reviews the structure and function of RPA, summarizes recent studies of RPA in DNA replication and other DNA processing pathways, and proposes a general model for the role of RPA in protein-mediated hand-off.

Publication types

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

MeSH terms

  • DNA / metabolism
  • DNA Replication / physiology*
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / physiology*
  • Models, Biological
  • Protein Conformation
  • Replication Protein A / chemistry
  • Replication Protein A / physiology*
  • Saccharomyces cerevisiae / genetics*


  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Replication Protein A
  • DNA