Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1

@article{De2004PuttingTP,
  title={Putting the pieces together: identification and characterization of structural domains in the V(D)J recombination protein RAG1},
  author={Pallabi De and Karla K. Rodgers},
  journal={Immunological Reviews},
  year={2004},
  volume={200}
}
Summary:  V(D)J recombination generates functional immunoglobulin and T‐cell receptor genes in developing lymphocytes. The recombination‐activating gene 1 (RAG1) and RAG2 proteins catalyze site‐specific DNA cleavage in this recombination process. Biochemical studies have identified catalytically active regions of each protein, referred to as the core regions. Here, we review our progress in the identification and characterization, in biophysical and biochemical terms, of topologically… 
Elucidating the domain architecture and functions of non-core RAG1: The capacity of a non-core zinc-binding domain to function in nuclear import and nucleic acid binding
TLDR
The CND alone, and in combination with other regions of non-core RAG1, functions in nuclear localization, zinc coordination, and interactions with nucleic acid, demonstrating the multiple roles that the non- core region can play in the function of the full length protein.
Structure of the RAG1 nonamer-binding domain with DNA reveals a dimer that mediates DNA synapsis
TLDR
The crystal structure of an essential DNA binding domain of the RAG1 catalytic core bound to its nonamer DNA recognition motif is reported, revealing a previously unsuspected function for the NBD in DNA synapsis and have implications for the regulation of DNA binding and cleavage by R AG1 and RAG2.
An interdomain boundary in RAG1 facilitates cooperative binding to RAG2 in formation of the V(D)J recombinase complex
TLDR
It is proposed that interaction of RAG2 with R AG1 induces cooperative interactions of multiple binding sites, induced through conformational changes at the RAG1 interdomain boundary, and resulting in formation of the DNA cleavage active site.
Peer Reviewed Title: Interaction of recombination signal sequences with RAG1 in V(D)J joining
TLDR
To have a more complete understanding of how RAG1 manipulates DNA strands containing the RSS, mRNA from the thymus of 15-day-old mice was extracted and it was discovered that the NBR domain of rRAG1 would only bind to the nanomer of the bottom 12- RSS strand.
V(D)J recombination: mechanisms of initiation.
TLDR
This review considers the functional significance of RAG-mediated histone recognition and ubiquitin ligase activities, and the role played by RAG in ensuring proper repair of DNA breaks made during V(D)J recombination, and proposes a model for the formation of R AG-DNA complexes.
RAG-Heptamer Interaction in the Synaptic Complex Is a Crucial Biochemical Checkpoint for the 12/23 Recombination Rule*
TLDR
It is proposed that the RAG-7-mer interaction is a critical step for coding DNA distortion and hairpin formation in the context of the 12/23 rule.
Identification and Characterization of a Gain-of-Function RAG-1 Mutant
TLDR
A novel RAG-1 mutation, E649A, is reported that supports elevated cleavage activity in vitro by preferentially enhancing hairpin formation and may interfere with the RAG proteins' ability to sense 12/23-regulated synapsis.
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References

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TLDR
Characterization of macromolecular interactions revealed that the central domain bound to the RSS with specificity for the heptamer and contained the predominant binding site for RAG2, while the C-terminal domain bound DNA cooperatively but did not show specificity for either conserved RSS element.
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TLDR
A model of RAG2 as a multimodular protein that utilizes one of its six faces for establishing productive contacts with RAG1 is supported, supported by deletion mapping and site-directed mutagenesis.
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TLDR
Results provide direct evidence that a C3HC4 motif is involved in a protein-protein interaction, in this case via homodimer formation, and have important implications for other C3 HC4-containing proteins.
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TLDR
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TLDR
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TLDR
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