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Molecular and Cellular Biology, June 2000, p. 4288-4294, Vol. 20, No. 12
Departments of Molecular Biology and Cell
Biology, The Scripps Research Institute, La Jolla, California 92037
Received 6 October 1999/Returned for modification 30 November
1999/Accepted 16 March 2000
Mitotic checkpoints restrain the onset of mitosis (M) when DNA is
incompletely replicated or damaged. These checkpoints are conserved
between the fission yeast Schizosaccharomyces pombe and
mammals. In both types of organisms, the methylxanthine caffeine overrides the synthesis (S)-M checkpoint that couples mitosis to
completion of DNA S phase. The molecular target of caffeine was sought
in fission yeast. Caffeine prevented activation of Cds1 and
phosphorylation of Chk1, two protein kinases that enforce the S-M
checkpoint triggered by hydroxyurea. Caffeine did not inhibit these
kinases in vitro but did inhibit Rad3, a kinase that regulates Cds1 and
Chk1. In accordance with this finding, caffeine also overrode the
G2-M DNA damage checkpoint that requires Rad3 function.
Rad3 coprecipitated with Cds1 expressed at endogenous amounts, a
finding that supports the hypothesis that Rad3 is involved in direct
activation of Cds1.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Mechanism of Caffeine-Induced Checkpoint Override in
Fission Yeast
*
Corresponding author. Mailing address: Department of
Molecular Biology, Scripps Research Institute, MB-3, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: (858) 784-8273. Fax: (858) 784-2265. E-mail: prussell{at}scripps.edu.
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