The bounty of RAGs: recombination signal complexes and reaction outcomes

Immunol Rev. 2004 Aug:200:90-114. doi: 10.1111/j.0105-2896.2004.00159.x.

Abstract

V(D)J recombination is a form of site-specific DNA rearrangement through which antigen receptor genes are assembled. This process involves the breakage and reunion of DNA mediated by two lymphoid cell-specific proteins, recombination activating genes RAG-1 and RAG-2, and ubiquitously expressed architectural DNA-binding proteins and DNA-repair factors. Here I review the progress toward understanding the composition, assembly, organization, and activity of the protein-DNA complexes that support the initiation of V(D)J recombination, as well as the molecular basis for the sequence-specific recognition of recombination signal sequences (RSSs) that are the targets of the RAG proteins. Parallels are drawn between V(D)J recombination and Tn5/Tn10 transposition with respect to the reactions, the proteins, and the protein-DNA complexes involved in these processes. I also consider the relative roles of the different sequence elements within the RSS in recognition, cleavage, and post-cleavage events. Finally, I discuss alternative DNA transactions mediated by the V(D)J recombinase, the protein-DNA complexes that support them, and factors and forces that control them.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Rearrangement, B-Lymphocyte*
  • Gene Rearrangement, T-Lymphocyte*
  • HMGB1 Protein / genetics
  • HMGB1 Protein / metabolism
  • HMGB2 Protein / genetics
  • HMGB2 Protein / metabolism
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein Sorting Signals
  • VDJ Recombinases / physiology

Substances

  • DNA-Binding Proteins
  • HMGB1 Protein
  • HMGB2 Protein
  • Homeodomain Proteins
  • Nuclear Proteins
  • Protein Sorting Signals
  • RAG2 protein, human
  • V(D)J recombination activating protein 2
  • RAG-1 protein
  • VDJ Recombinases