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A more recent version of this article appeared on March 1, 2002
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Submitted on July 24, 2001
Revised on November 1, 2001
Accepted on December 4, 2001
1 Wellcome/CRC Institute, Tennis Court Road, and Department of Zoology, University of Cambridge, Cambridge, CB2 1QR, United Kingdom
* Corresponding author. E-mail address: mrj{at}mole.bio.cam.ac.uk.
Cyclins A and E and their partner cyclin-dependent kinases (Cdk) are key regulators of DNA synthesis and of mitosis. Immunofluorescence studies have shown that both cyclins are nuclear, and that a proportion of cyclin A is localised to sites of DNA replication. However, recently both cyclin A and cyclin E have been implicated as regulators of centrosome replication and it is unclear when and where these cyclin-Cdks can interact with cytoplasmic substrates. We have used live cell imaging to study the behaviour of cyclin/Cdk complexes. We find that cyclin A and cyclin E are able to regulate both nuclear and cytoplasmic events because they both shuttle between the nucleus and the cytoplasm. However, we find that there are marked differences in their shuttling behaviour that raise the possibility that cyclin/Cdk function could be regulated at the level of nuclear import and export. In the course of these experiments we have also found that, contrary to published results, mutations in the hydrophobic patch of cyclin A do affect Cdk binding and nuclear import. This has implications for the role of the hydrophobic patch as a substrate selection motif.
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