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

Accumulation of the V(D)J recombinase protein RAG-P 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 p27(Kip1) and related CDK inhibitors. Coinduction of RAG-P and G1 delay by p27(Kip1) 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. p27(Kip1) may stimulate V(D)J recombination by coordinating accumulation of RAGE 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.