Cell cycle regulation of V(D)J recombination-activating protein RAG-2

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • B-Lymphocytes / metabolism*
  • Cell Cycle / drug effects*
  • Cell Line
  • DNA-Binding Proteins*
  • Flow Cytometry
  • G1 Phase / physiology
  • Gene Expression Regulation*
  • Gene Rearrangement, B-Lymphocyte
  • Hematopoietic Stem Cells
  • Mice
  • Proteins / metabolism
  • Proteins / pharmacology*
  • RNA, Messenger / analysis
  • Resting Phase, Cell Cycle / physiology
  • Thymus Gland / cytology
  • Thymus Gland / metabolism*


  • DNA-Binding Proteins
  • Proteins
  • RNA, Messenger
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2