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A more recent version of this article appeared on March 10, 2006
Papers In Press, published online ahead of print January 9, 2006
J. Biol. Chem, 10.1074/jbc.M512705200
Submitted on November 28, 2005
Revised on January 9, 2006
Accepted on January 9, 2006
PCNA is a co-factor for Cdt1 degradation by CUL4/DDB1 mediated N-terminal ubiquitination
Takeshi Senga, Umasundari Sivaprasad, Wenge Zhu, Jong Hoon Park, Emily E. Arias, Johannes C. Walter, and Anindya Dutta
Biochemistry and Mol. Gen., University of Virginia Health Sciences System, Charlottesville, VA 22908
Corresponding Author: ad8q{at}virginia.edu
Cdt1, a protein essential in G1 for licensing of origins for DNA replication, is inhibited in S phase both by binding to geminin and degradation by proteasomes. Cdt1 is also degraded after DNA damage in order to stop licensing of new origins until after DNA repair. Phosphorylation of Cdt1 by cyclin dependent kinases promotes its binding to Skp2-SCF E3 ubiquitin ligase, but the Cdk2/Skp2 mediated pathway is not essential for the degradation of Cdt1. Here we show that the N-terminus of Cdt1 contains a second degradation signal that is active after DNA damage and in S-phase and is dependent on the interaction of Cdt1 with PCNA through a PCNA binding motif. The degradation involves N terminal ubiquitination and requires Cul4 and Ddb1 proteins, components of an E3 ubiquitin ligase implicated in protein degradation after DNA damage. Therefore PCNA, the match-maker for many proteins involved in DNA and chromatin metabolism, also serves to promote the targeted degradation of associated proteins in S phase or after DNA damage.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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