Abstract
V(D)J RECOMBINATION, the process that assembles antigen-receptor genes, is directed by signal sequences flanking the DNA segments to be joined. Signals consist of a conserved heptamer and nonamer separated by a spacer of either 12 or 23 base pairs. Recombination occurs almost exclusively between two signals with spacers of different lengths. This restriction, called the '12/ 23 rule', governs the organization and pattern of rearrangement of antigen-receptor loci1,2. In vitro work demonstrating the direct roles of the Rag proteins in the initiation of V(D)J recombination did not recreate the 12/23 rule3,4. Instead, double-strand breaks were formed efficiently at isolated signals. Here we show that extracts made from a lymphoid cell line that expresses truncated forms of the Ragl and Rag2 proteins have a signal-cutting activity that obeys the 12/23 rule. Cleavage at the two signals is concerted and requires their synapsis, and mutations of one signal prevent cleavage at both.
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Eastman, Q., Leu, T. & Schatz, D. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature 380, 85–88 (1996). https://doi.org/10.1038/380085a0
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DOI: https://doi.org/10.1038/380085a0
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