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 journalArticlepeer-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 languageEnglish (US)
Pages (from-to)699-709
Number of pages11
JournalMolecular cell
Volume18
Issue number6
DOIs
StatePublished - Jun 10 2005
Externally publishedYes

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

Fingerprint

Dive into the research topics of 'Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle'. Together they form a unique fingerprint.

Cite this