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Science 4 December 1998:
Vol. 282. no. 5395, pp. 1886 - 1889
DOI: 10.1126/science.282.5395.1886
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Reports

Coupling of Mitosis to the Completion of S Phase Through Cdc34-Mediated Degradation of Wee1

W. Matthew Michael, * John Newport

The dependence of mitosis on the completion of the period of DNA replication in the cell cycle [synthesis (S) phase] ensures that chromosome segregation occurs only after the genome has been fully duplicated. A key negative regulator of mitosis, the protein kinase Wee1, was degraded in a Cdc34-dependent fashion in Xenopus egg extracts. This proteolysis event was required for a timely entrance into mitosis and was inhibited when DNA replication was blocked. Therefore, the DNA replication checkpoint can prevent mitosis by suppressing the proteolysis of Wee1 during S phase.

Department of Biology, University of California, San Diego, La Jolla, CA 92093-0347, USA.
*   To whom correspondence should be addressed. E-mail: wmichael{at}biomail.ucsd.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Arabidopsis WEE1 Kinase Controls Cell Cycle Arrest in Response to Activation of the DNA Integrity Checkpoint.
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The Function and Regulation of Budding Yeast Swe1 in Response to Interrupted DNA Synthesis.
H. Liu and Y. Wang (2006)
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J. S. Stanford and J. V. Ruderman (2005)
Mol. Biol. Cell 16, 5749-5760
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DNA replication checkpoint control of Wee1 stability by vertebrate Hsl7.
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DNA replication is required for the checkpoint response to damaged DNA in Xenopus egg extracts.
M. P. Stokes, R. Van Hatten, H. D. Lindsay, and W. M. Michael (2002)
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W.-H. Shen, Y. Parmentier, H. Hellmann, E. Lechner, A. Dong, J. Masson, F. Granier, L. Lepiniec, M. Estelle, and P. Genschik (2002)
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L. M. Topper, H. Bastians, J. V. Ruderman, and G. J. Gorbsky (2001)
J. Cell Biol. 154, 707-718
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Roles of the Mitotic Inhibitors Wee1 and Mik1 in the G2 DNA Damage and Replication Checkpoints.
N. Rhind and P. Russell (2001)
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Y. Wang, C. Jacobs, K. E. Hook, H. Duan, R. N. Booher, and Y. Sun (2000)
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M. Masuda, Y. Nagai, N. Oshima, K. Tanaka, H. Murakami, H. Igarashi, and H. Okayama (2000)
J. Virol. 74, 2636-2646
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Absence of Wee1 ensures the meiotic cell cycle in Xenopus oocytes.
N. Nakajo, S. Yoshitome, J. Iwashita, M. Iida, K. Uto, S. Ueno, K. Okamoto, and N. Sagata (2000)
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H Kawahara, R Philipova, H Yokosawa, R Patel, K Tanaka, and M Whitaker (2000)
J. Cell Sci. 113, 2659-2670
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Association of human ubiquitin-conjugating enzyme CDC34 with the mitotic spindle in anaphase.
F Reymond, C Wirbelauer, and W Krek (2000)
J. Cell Sci. 113, 1687-1694
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The G(2) DNA damage checkpoint targets both Wee1 and Cdc25.
J. Raleigh and M. O'Connell (2000)
J. Cell Sci. 113, 1727-1736
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Regulation of Mitotic Inhibitor Mik1 Helps to Enforce the DNA Damage Checkpoint.
B. A. Baber-Furnari, N. Rhind, M. N. Boddy, P. Shanahan, A. Lopez-Girona, and P. Russell (2000)
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Mol. Biol. Cell 10, 3661-3674
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Cell Cycle-regulated Proteolysis of Mitotic Target Proteins.
H. Bastians, L. M. Topper, G. L. Gorbsky, and J. V. Ruderman (1999)
Mol. Biol. Cell 10, 3927-3941
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The Morphogenesis Checkpoint in Saccharomyces cerevisiae: Cell Cycle Control of Swe1p Degradation by Hsl1p and Hsl7p.
J. N. McMillan, M. S. Longtine, R. A. L. Sia, C. L. Theesfeld, E. S. G. Bardes, J. R. Pringle, and D. J. Lew (1999)
Mol. Cell. Biol. 19, 6929-6939
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A quantitative analysis of the kinetics of the G2 DNA damage checkpoint system.
B. D. Aguda (1999)
PNAS 96, 11352-11357
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Cdc25 Inhibited In Vivo and In Vitro by Checkpoint Kinases Cds1 and Chk1.
B. Furnari, A. Blasina, M. N. Boddy, C. H. McGowan, and P. Russell (1999)
Mol. Biol. Cell 10, 833-845
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Characterization of maize (Zea mays L.) Wee1 and its activity in developing endosperm.
Y. Sun, B. P. Dilkes, C. Zhang, R. A. Dante, N. P. Carneiro, K. S. Lowe, R. Jung, W. J. Gordon-Kamm, and B. A. Larkins (1999)
PNAS 96, 4180-4185
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