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

@article{Jones2004TheTO,
  title={The taming of a transposon: V(D)J recombination and the immune system},
  author={Jessica M Jones and Martin Gellert},
  journal={Immunological Reviews},
  year={2004},
  volume={200}
}
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… 
The Happy Hopping of Transposons: The Origins of V(D)J Recombination in Adaptive Immunity
TLDR
This review follows the evolution of recombination activation genes (RAGs), components of adaptive immunity, from TEs, focusing on the structural and mechanistic similarities between RAG recombinases and DNA transposases.
New insights into the evolutionary origins of the recombination‐activating gene proteins and V(D)J recombination
TLDR
Recent progress in identifying and characterizing RAG‐like proteins and the TEs that encode them is summarized and a refined model for the evolution of V(D)J recombination and the RAG proteins is presented.
Transposon Molecular Domestication and the Evolution of the RAG Recombinase
TLDR
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.
TLDR
It is proposed that evolution of RAG1/RAG2 began with a Transib transposon whose intrinsic recombination activity was enhanced by capture of an ancestral RAG2, allowing for the development of adaptive immunity.
Chromosomal reinsertion of broken RSS ends during T cell development
TLDR
The noncore domain of RAG2 serves to limit the extent to which the integrity of the genome is threatened by mistargeting of V(D)J recombination, as seen in murine thymocyte and splenocyte genomic DNA samples.
The DDE recombinases: diverse roles in acquired and innate immunity.
  • D. Dreyfus
  • Biology, Medicine
    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
  • 2006
Paleo-Immunology: Evidence Consistent with Insertion of a Primordial Herpes Virus-Like Element in the Origins of Acquired Immunity
TLDR
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.
TLDR
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.
  • P. Rice
  • Biology
    Genes & development
  • 2005
TLDR
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.
...
...

References

SHOWING 1-10 OF 130 REFERENCES
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
TLDR
The results support the theory that RAG1 and RAG2 were once components of a transposable element, and that the split nature of immunoglobulin and T-cell-receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates.
Analysis of regions of RAG-2 important for V(D)J recombination.
TLDR
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.
  • M. Gellert
  • Biology
    Annual review of biochemistry
  • 2002
TLDR
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
TLDR
The RAG proteins are capable of mediating all necessary breakage and joining events on both partner chromosomes; thus, the V(D)J recombinase may be far more culpable for oncogenic translocations than has been suspected.
RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.
The vast repertoire of immunoglobulins and T cell receptors is generated, in part, by V(D)J recombination, a series of genomic rearrangements that occur specifically in developing lymphocytes. The
In vivo transposition mediated by V(D)J recombinase in human T lymphocytes
TLDR
Evidence is presented of in vivo inter‐chromosomal transposition in humans mediated by V(D)J recombinase‐mediated transposition as a mutagenic mechanism capable of deleterious genetic rearrangements in humans.
Definition of a core region of RAG-2 that is functional in V(D)J recombination.
TLDR
This work constructed mutated RAG-2 genes and examined their ability to support recombination of plasmid substrates in a fibroblast cell line and found that all basic features of V(D)J joining are retained in a R AG-2 protein with only the first 75% of the sequence.
Dual role of RAG2 in V(D)J recombination: catalysis and regulation of ordered Ig gene assembly
TLDR
It is shown that the C‐terminus of the RAG2 protein, although dispensable for the basic recombination reaction and for Ig heavy chain DH to JH joining, is essential for efficient VH to DJH rearrangement at the IgH locus.
Expression and V(D)J recombination activity of mutated RAG-1 proteins.
TLDR
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.
...
...