TY - JOUR
T1 - A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle
AU - Li, Zhong
AU - Dordai, Dominic I.
AU - Lee, Jinhak
AU - Desiderio, Stephen
N1 - Funding Information:
We thank James Flook (The Johns Hopkins University) for assistance in fluorescence cytometry and Jean Richa (University of Pennsylvania) for assistance in the generation of transgenic mice. We are grateful to Weei-Chin Lin (Duke University) and Mark Schlissel (The Johns Hopkins University) for stimulating discussions. This work was supported by the Howard Hughes Medical Institute and by a grant from the National Cancer Institute.
PY - 1996/12
Y1 - 1996/12
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(00)80272-1
DO - 10.1016/S1074-7613(00)80272-1
M3 - Article
C2 - 8986717
AN - SCOPUS:0030498092
SN - 1074-7613
VL - 5
SP - 575
EP - 589
JO - Immunity
JF - Immunity
IS - 6
ER -