• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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.

Pubmed ID: 15949444

Authors

  • Jiang H
  • Chang FC
  • Ross AE
  • Lee J
  • Nakayama K
  • Nakayama K
  • Desiderio S

Journal

Molecular cell

Publication Data

June 10, 2005

Associated Grants

None

Mesh Terms

  • Cell Cycle
  • DNA-Binding Proteins
  • G1 Phase
  • HeLa Cells
  • Humans
  • Nuclear Proteins
  • Recombination, Genetic
  • S Phase
  • S-Phase Kinase-Associated Proteins
  • Ubiquitin
  • VDJ Recombinases