Lin W C, Desiderio S
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2733-7. doi: 10.1073/pnas.91.7.2733.
The antigen receptors of B and T lymphocytes are encoded in multiple germ-line DNA segments that are joined during lymphocyte development. The recombination-activating proteins RAG-1 and RAG-2 are both essential 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 associated with its rapid degradation. In an immature B-cell line and in normal thymocytes, RAG-2 protein accumulates preferentially in the G0/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 throughout the S, G2, and M phases. The amount of RAG-1 protein shows considerably less fluctuation. The variation in RAG-2 protein is likely to be established, at least in part, by a posttranscriptional mechanism. These observations suggest that V(D)J rearrangement occurs entirely or preferentially within G0/G1.
B淋巴细胞和T淋巴细胞的抗原受体由多个种系DNA片段编码，这些片段在淋巴细胞发育过程中连接在一起。重组激活蛋白RAG-1和RAG-2对于这个称为V(D)J重排的过程都是必不可少的。RAG-2蛋白在苏氨酸490位点被一种或多种细胞周期蛋白依赖性激酶磷酸化与其快速降解有关。在一个未成熟的B细胞系和正常胸腺细胞中，RAG-2蛋白优先在细胞周期的G0/G1期积累，并在细胞进入S期前下降至少20倍。在整个S期、G2期和M期，RAG-2蛋白的量都保持在较低水平。RAG-1蛋白的量波动较小。RAG-2蛋白的变化可能至少部分是由转录后机制决定的。这些观察结果表明，V(D)J重排完全或优先发生在G0/G1期。
