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RAG: a recombinase diversified

Abstract

During B cell and T cell development, the lymphoid-specific proteins RAG-1 and RAG-2 act together to initiate the assembly of antigen receptor genes through a series of site-specific somatic DNA rearrangements that are collectively called variable-diversity-joining (V(D)J) recombination. In the past 20 years, a great deal has been learned about the enzymatic activities of the RAG-1–RAG-2 complex. Recent studies have identified several new and exciting regulatory functions of the RAG-1–RAG-2 complex. Here we discuss some of these functions and suggest that the RAG-1–RAG-2 complex nucleates a specialized subnuclear compartment that we call the 'V(D)J recombination factory'.

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Figure 1: Multilayered regulation of V(D)J recombination.
Figure 2: Model of a putative V(D)J recombination factory.

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Acknowledgements

We apologize to those whose work we were unable to cite because of space limitations. Supported by the US National Institutes of Health (M.A.O.) and the Damon Runyon Cancer Research Foundation (DRG-1981-08 to A.G.W.M.).

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Matthews, A., Oettinger, M. RAG: a recombinase diversified. Nat Immunol 10, 817–821 (2009). https://doi.org/10.1038/ni.1776

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