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Nucleic Acids Research 2005 33(1):316-324; doi:10.1093/nar/gki176
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Published online 13 January 2005

© 2005, the authors Nucleic Acids Research, Vol. 33 No. 1 © Oxford University Press 2005; all rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use permissions, please contact journals.permissions{at}oupjournals.org.

Article

Functional domains of the Xenopus replication licensing factor Cdt1

Andrew Ferenbach, Anatoliy Li, Marta Brito-Martins and J. Julian Blow*

Wellcome Trust Biocentre, University of Dundee Dow Street, Dundee DD1 5EH, UK

*To whom correspondence should be addressed. Tel: +44 1382 345797; Fax: +44 1382 348072; Email: j.j.blow{at}dundee.ac.uk

Received November 25, 2004. Revised December 20, 2004. Accepted December 20, 2004.

During late mitosis and early G1, replication origins are licensed for subsequent replication by loading heterohexamers of the mini-chromosome maintenance proteins (Mcm2-7). To prevent re-replication of DNA, the licensing system is down-regulated at other cell cycle stages. A small protein called geminin plays an important role in this down-regulation by binding and inhibiting the Cdt1 component of the licensing system. We examine here the organization of Xenopus Cdt1, delimiting regions of Cdt1 required for licensing and regions required for geminin interaction. The C-terminal 377 residues of Cdt1 are required for licensing and the extreme C-terminus contains a domain that interacts with an Mcm(2,4,6,7) complex. Two regions of Cdt1 interact with geminin: one at the N-terminus, and one in the centre of the protein. Only the central region binds geminin tightly enough to successfully compete with full-length Cdt1 for geminin binding. This interaction requires a predicted coiled-coil domain that is conserved amongst metazoan Cdt1 homologues. Geminin forms a homodimer, with each dimer binding one molecule of Cdt1. Separation of the domains necessary for licensing activity from domains required for a strong interaction with geminin generated a construct, whose licensing activity was partially insensitive to geminin inhibition.

Present address: Marta Brito-Martins, National Heart and Lung Institute, Cardiac Medicine Department, Imperial College, Dovehouse Street, SW3 6LY London, UK


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