Due to necessary maintenance, Xenbase will be unavailable December 24-30, 2014. We apologize for the inconvenience.

Click on this message to dismiss it.
Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
XB-ART-924
Nat Cell Biol. January 1, 2006; 8 (1): 84-90.

PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication.

Arias EE , Walter JC .


Abstract
Ubiquitin-mediated proteolysis of the replication licensing factor Cdt1 (Cdc10-dependent transcript 1) in S phase is a key mechanism that limits DNA replication to a single round per cell cycle in metazoans. In Xenopus egg extracts, Cdt1 is destroyed on chromatin during DNA replication. Here, we report that replication-dependent proteolysis of Cdt1 requires its interaction with proliferating cell nuclear antigen (PCNA), a homotrimeric processivity factor for DNA polymerases. Cdt1 binds to PCNA through a consensus PCNA-interaction motif that is conserved in Cdt1 of all metazoans, and removal of PCNA from egg extracts inhibits replication-dependent Cdt1 destruction. Mutation of the PCNA-interaction motif yields a stabilized Cdt1 protein that induces re-replication. DDB1, a component of the Cul4 E3 ubiquitin ligase that mediates human Cdt1 proteolysis in response to DNA damage, is also required for replication-dependent Cdt1 destruction. Cdt1 and DDB1 interact in extracts, and DDB1 chromatin loading is dependent on the binding of Cdt1 to PCNA, which indicates that PCNA docking activates the pre-formed Cdt1-Cul4(DDB1) ligase complex. Thus, PCNA functions as a platform for Cdt1 destruction, ensuring efficient and temporally restricted inactivation of a key cell-cycle regulator.

PubMed ID: 16362051
Article link: Nat Cell Biol.

Genes referenced: cdt1 ddb1 pcna sept7
Antibodies referenced:
Morpholinos referenced:

My Xenbase: [ Log-in / Register ]
version: [3.3.1]


Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556