Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle

Hao Jiang, Fu Chung Chang, Ashley E. Ross, Jihyun Lee, Keiichi Nakayama, Keiko Nakayama, Stephen Desiderio

研究成果: ジャーナルへの寄稿記事

85 引用 (Scopus)

抄録

The periodic destruction of RAG-2 at the G1-to-S transition couples V(D)J recombination to the G0 and G1 cell cycle phases and coordinates RAG-mediated DNA cleavage with DNA repair by nonhomologous end joining. To define the mechanism by which this occurs, we reproduced cell cycle-dependent regulation of the V(D)J recombinase in a cell-free system. The ubiquitin-proteasomal pathway carries out destruction of RAG-2 in lysates of S phase cells and during S phase in vivo. Remarkably, the Skp2-SCF ubiquitin ligase, which plays a central role in cell cycle regulation through the destruction of p27, mediates ubiquitylation of RAG-2 in vitro and degradation of RAG-2 in vivo. The regulation of antigen receptor gene assembly by Skp2-SCF provides an unexpected and direct mechanistic link between DNA recombination and the cell cycle.

元の言語英語
ページ(範囲)699-709
ページ数11
ジャーナルMolecular Cell
18
発行部数6
DOI
出版物ステータス出版済み - 6 10 2005

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VDJ Recombinases
Ubiquitination
Cell Cycle
S Phase
SKP Cullin F-Box Protein Ligases
DNA End-Joining Repair
V(D)J Recombination
DNA Cleavage
Antigen Receptors
Cell-Free System
Ubiquitin
Genetic Recombination
DNA
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

これを引用

Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle. / Jiang, Hao; Chang, Fu Chung; Ross, Ashley E.; Lee, Jihyun; Nakayama, Keiichi; Nakayama, Keiko; Desiderio, Stephen.

:: Molecular Cell, 巻 18, 番号 6, 10.06.2005, p. 699-709.

研究成果: ジャーナルへの寄稿記事

Jiang, Hao ; Chang, Fu Chung ; Ross, Ashley E. ; Lee, Jihyun ; Nakayama, Keiichi ; Nakayama, Keiko ; Desiderio, Stephen. / Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle. :: Molecular Cell. 2005 ; 巻 18, 番号 6. pp. 699-709.
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abstract = "The periodic destruction of RAG-2 at the G1-to-S transition couples V(D)J recombination to the G0 and G1 cell cycle phases and coordinates RAG-mediated DNA cleavage with DNA repair by nonhomologous end joining. To define the mechanism by which this occurs, we reproduced cell cycle-dependent regulation of the V(D)J recombinase in a cell-free system. The ubiquitin-proteasomal pathway carries out destruction of RAG-2 in lysates of S phase cells and during S phase in vivo. Remarkably, the Skp2-SCF ubiquitin ligase, which plays a central role in cell cycle regulation through the destruction of p27, mediates ubiquitylation of RAG-2 in vitro and degradation of RAG-2 in vivo. The regulation of antigen receptor gene assembly by Skp2-SCF provides an unexpected and direct mechanistic link between DNA recombination and the cell cycle.",
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AU - Jiang, Hao

AU - Chang, Fu Chung

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AU - Lee, Jihyun

AU - Nakayama, Keiichi

AU - Nakayama, Keiko

AU - Desiderio, Stephen

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AB - The periodic destruction of RAG-2 at the G1-to-S transition couples V(D)J recombination to the G0 and G1 cell cycle phases and coordinates RAG-mediated DNA cleavage with DNA repair by nonhomologous end joining. To define the mechanism by which this occurs, we reproduced cell cycle-dependent regulation of the V(D)J recombinase in a cell-free system. The ubiquitin-proteasomal pathway carries out destruction of RAG-2 in lysates of S phase cells and during S phase in vivo. Remarkably, the Skp2-SCF ubiquitin ligase, which plays a central role in cell cycle regulation through the destruction of p27, mediates ubiquitylation of RAG-2 in vitro and degradation of RAG-2 in vivo. The regulation of antigen receptor gene assembly by Skp2-SCF provides an unexpected and direct mechanistic link between DNA recombination and the cell cycle.

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