A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle

Zhong Li, Dominic I. Dordai, Jinhak Lee, Stephen Desiderio

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

The proteins RAG-1 and RAG-2 are essential for initiation of V(D)J recombination. In dividing cells, RAG-2 accumulates during G1 and is undetectable during the S and G2/M cell cycle phases. A conserved degradation signal, including an essential CDK phosphorylation site at Thr-490, regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. Mutations within this signal abolish periodic degradation of RAG-2 protein in dividing cells. In mice expressing endogenous or wild-type transgenic RAG-2, V(D)J recombination intermediates accumulate preferentially in G0/G1 thymocytes; this restriction is relieved by mutation of Thr-490 to alanine (T490A). Thus, periodic destruction of RAG-2 protein couples V(D)J recombination to cell cycle phase. Using transgenic mice expressing the T490A RAG-2 mutant and a functional T cell receptor β chain, we demonstrate that coupling of V(D)J recombination to the cell cycle is not essential for enforcement of allelic exclusion.

Original languageEnglish (US)
Pages (from-to)575-589
Number of pages15
JournalImmunity
Volume5
Issue number6
DOIs
StatePublished - Dec 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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