The taming of a transposon: V(D)J recombination and the immune system

  title={The taming of a transposon: V(D)J recombination and the immune system},
  author={Jessica M Jones and Martin Gellert},
  journal={Immunological Reviews},
Summary:  The genes that encode immunoglobulins and T‐cell receptors must be assembled from the multiple variable (V), joining (J), and sometimes diversity (D) gene segments present in the germline loci. This process of V(D)J recombination is the major source of the immense diversity of the immune repertoire of jawed vertebrates. The recombinase that initiates the process, recombination‐activating genes 1 (RAG1) and RAG2, belongs to a large family that includes transposases and retroviral… 
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Transposon Molecular Domestication and the Evolution of the RAG Recombinase
A two-tiered mechanism for the suppression of RAG-mediated transposition is revealed, the evolution of V(D)J recombination is illuminated, and insight is provided into the principles that govern the molecular domestication of transposons.
Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination.
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Chromosomal reinsertion of broken RSS ends during T cell development
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The suggestion that the DDE recombinase responsible for the origins of acquired immunity was encoded by a primordial herpes virus, rather than a “RAG transposon” is suggested.
Large-scale chromatin remodeling at the immunoglobulin heavy chain locus: a paradigm for multigene regulation.
This chapter will examine the structure of the Igh locus and the large-scale and higher-order chromatin remodelling processes associated with V(D)J recombination, at the level of the locus itself, its conformational changes and its dynamic localisation within the nucleus.
Visualizing Mu transposition: assembling the puzzle pieces.
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An electron microscopy-based 3D model of the protein–DNA complex responsible for Mu transposition (the transpososome) is presented, which not only ties together years of accumulated biochemical and structural data, but also provides interesting new insights.


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Analysis of regions of RAG-2 important for V(D)J recombination.
Although the RAG-2 protein shows extensive evolutionary conservation across its length, it is found that the carboxy-terminal portion of R AG-2, including an acidic region, is dispensable for all forms of recombination tested.
V(D)J recombination: RAG proteins, repair factors, and regulation.
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V(D)J recombination is strongly regulated by limiting access to RSS sites within chromatin, so that particular sites are available only in certain cell types and developmental stages, and the roles of enhancers, histone acetylation, and chromatin remodeling factors in controlling accessibility are discussed.
Targeted Transposition by the V(D)J Recombinase
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RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.
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Definition of a core region of RAG-2 that is functional in V(D)J recombination.
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Expression and V(D)J recombination activity of mutated RAG-1 proteins.
The sequences encoding mouse RAG-1 are explored by deleting large parts of the gene and by introducing local sequence changes and it is found that a R AG-1 gene with 40% of the coding region deleted still retains its recombination function.