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. 2017 Aug 30;18(9):1876. doi: 10.3390/ijms18091876

Figure 4.

Figure 4

DNA damage regulates the expression of RAG1/2 through activation of the DDR. Cleavage of recombination signal sequences (RSS) by the recombination activating gene 1/2 complex (RAG1/2) (shown in green and red) in the Ig loci activates the ataxia telangiectasia mutated (ATM) kinase, which triggers a negative feedback loop involving the dissociation of forkhead box O1 (FOXO1) from the Erag enhancer in the RAG1/2 locus, and the induction of the NF-κB essential modulator (NEMO), shutting off RAG1/2 transcription. In parallel, a p53-dependent apoptotic response is triggered, which is counteracted by the B-cell lymphoma 6 (BCL6) protein to allow recombination to take place. At the same time, an NF-κB-dependent gene expression program that includes several key B-cell differentiation and survival genes is activated by ATM (indicated in the black frame). Arrows represent positive regulation (activation); T-bars represent negative regulation (inhibition).