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Science 287 (5458): 1644-1647
Copyright © 2000 by the American Association for the Advancement of Science
Requirement of the Prolyl Isomerase Pin1 for the Replication Checkpoint
Katharine E. Winkler,
Katherine I. Swenson,
Sally Kornbluth,
Anthony R. Means
*
The peptidyl-prolyl isomerase Pin1 has been implicated in
regulating cell cycle progression. Pin1 was found to be required for
the DNA replication checkpoint in Xenopus laevis. Egg
extracts depleted of Pin1 inappropriately transited from the
G2 to the M phase of the cell cycle in the presence of the
DNA replication inhibitor aphidicolin. This defect in replication
checkpoint function was reversed after the addition of recombinant
wild-type Pin1, but not an isomerase-inactive mutant, to the depleted
extract. Premature mitotic entry in the absence of Pin1 was accompanied by hyperphosphorylation of Cdc25, activation of Cdc2/cyclin
B, and generation of epitopes recognized by the mitotic phosphoprotein antibody, MPM-2. Therefore, Pin1 appears to be required for the checkpoint delaying the onset of mitosis in response to incomplete replication.
Department of Pharmacology and Cancer Biology, Duke University
Medical Center, Box 3813, Durham, NC 27710, USA.
*
To whom correspondence should be addressed. E-mail:
means001{at}mc.duke.edu
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