CELL-CYCLE REGULATION OF V(D)J RECOMBINATION-ACTIVATING PROTEIN RAG-2

The antigen receptors of B and T lymphocytes are encoded in multiple g erm-line DNA segments that are joined during lymphocyte development. T he recombination-activating proteins RAG-1 and RAG-2 are both essentia l for this process, termed V(D)J rearrangement. Phosphorylation of the RAG-2 protein at Thr-490 by one or more cyclin-dependent kinases is a ssociated with its rapid degradation. In an immature B-cell line and i n normal thymocytes, RAG-2 protein accumulates preferentially in the G 0/G1 phases of the cell cycle and declines by at least 20-fold before cells enter S phase. The amount of RAG-2 protein remains low throughou t the S, G2, and M phases. The amount of RAG-1 protein shows considera bly less fluctuation. The variation in RAG-2 protein is likely to be e stablished, at least in part, by a posttranscriptional mechanism. Thes e observations suggest that V(D)J rearrangement occurs entirely or pre ferentially within G0/G1.