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Immunity. 1999 Dec;11(6):771-81.

Cyclin A/CDK2 regulates V(D)J recombination by coordinating RAG-2 accumulation and DNA repair.

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Department of Molecular Biology and Genetics and Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.


Accumulation of the V(D)J recombinase protein RAG-2 is restricted to G0/G1 cells by phosphorylation-mediated degradation at the G1-S boundary. Here cyclin A/CDK2 is shown to oppose RAG-2 accumulation; conversely, RAG-2 is induced by p27Kip1 and related CDK inhibitors. Coinduction of RAG-2 and G1 delay by p27Kip1 is accompanied by strong stimulation of V(D)J recombination. Unexpectedly, induction of RAG-2 accumulation in the absence of G1 delay has no effect on recombination frequency. p27Kip1 may stimulate V(D)J recombination by coordinating accumulation of RAG-2 with prolongation of G1, when nonhomologous end joining is preferentially active. Consistent with this, enforced expression of RAG-2 throughout cell cycle is associated with accumulation of aberrant recombination products reminiscent of those formed in the absence of nonhomologous end joining.

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