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

doi:10.1016/j.molcel.2005.05.011

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

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.

Original language	English (US)
Pages (from-to)	699-709
Number of pages	11
Journal	Molecular cell
Volume	18
Issue number	6
DOIs	https://doi.org/10.1016/j.molcel.2005.05.011
State	Published - Jun 10 2005
Externally published	Yes

Funding

We thank Dr. H. Zhang for baculoviruses encoding Skp2 and Cul1 and Dr. D. Bohmann for the ubiquitin-HA construct. This work was supported by the National Cancer Institute and the Howard Hughes Medical Institute.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2005.05.011

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

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.",

author = "Hao Jiang and Chang, {Fu Chung} and Ross, {Ashley E.} and Jihyun Lee and Keiichi Nakayama and Keiko Nakayama and Stephen Desiderio",

note = "Funding Information: We thank Dr. H. Zhang for baculoviruses encoding Skp2 and Cul1 and Dr. D. Bohmann for the ubiquitin-HA construct. This work was supported by the National Cancer Institute and the Howard Hughes Medical Institute. ",

year = "2005",

month = jun,

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doi = "10.1016/j.molcel.2005.05.011",

language = "English (US)",

volume = "18",

pages = "699--709",

journal = "Molecular cell",

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T1 - Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle

AU - Jiang, Hao

AU - Chang, Fu Chung

AU - Ross, Ashley E.

AU - Lee, Jihyun

AU - Nakayama, Keiichi

AU - Nakayama, Keiko

AU - Desiderio, Stephen

N1 - Funding Information: We thank Dr. H. Zhang for baculoviruses encoding Skp2 and Cul1 and Dr. D. Bohmann for the ubiquitin-HA construct. This work was supported by the National Cancer Institute and the Howard Hughes Medical Institute.

PY - 2005/6/10

Y1 - 2005/6/10

N2 - 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.

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

Abstract

Funding

ASJC Scopus subject areas

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