Epigenetics Drives RAGs to Recombination Riches

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Epigenetics Drives RAGs to Recombination Riches Mark S. Schlissel  Cell  Volume 141, Issue 3, Pages 400-402 (April 2010) DOI: 10.1016/j.cell.2010.04.014 Copyright © 2010 Elsevier Inc. Terms and Conditions

Figure 1 RAG Proteins and V(D)J Recombination. The RAG1 and RAG2 proteins, coexpressed exclusively in T and B lymphocytes, exist in these cells as either individual proteins or as parts of multimeric complexes. These proteins form the recombinase that, along with a set of widely expressed DNA break repair factors, mediates V(D)J recombination. In this process, the variable domains of the antigen receptors of B and T lymphocytes are assembled from component V, D, and J gene segments during lymphocyte development. (A) RAG2 binds to a H3K4me3-modified nucleosome and RAG1 binds to a recombination signal sequence (RSS) that flanks a rearranging gene segment. The interaction of RAG2 with H3K4me3 induces an allosteric change in the active site of RAG1 (arrow), leading to DNA cleavage at the RSS-gene segment border. (B) RAG2 binds to H3K4me3-modified nucleosomes at transcribed regions throughout the genome, but RAG1 is not present at these sites so DNA cleavage does not occur. (C) RAG1 can bind on its own to RSS DNA, but does not catalyze DNA cleavage as RAG2 is absent. Cell 2010 141, 400-402DOI: (10.1016/j.cell.2010.04.014) Copyright © 2010 Elsevier Inc. Terms and Conditions