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Molecular and Cellular Biology, June 1999, p. 4270-4278, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cell Cycle Regulation of DNA Replication Initiator Factor Dbf4p

Liang Cheng, Tim Collyer, and Christopher F. J. Hardy*

Department of Cell Biology and Physiology and Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110

Received 9 October 1998/Returned for modification 25 November 1998/Accepted 9 March 1999

The precise duplication of eukaryotic genetic material takes place once and only once per cell cycle and is dependent on the completion of the previous mitosis. Two evolutionarily conserved kinases, the cyclin B (Clb)/cyclin-dependent kinase (Cdk/Cdc28p) and Cdc7p along with its interacting factor Dbf4p, are required late in G1 to initiate DNA replication. We have determined that the levels of Dbf4p are cell cycle regulated. Dbf4p levels increase as cells begin S phase and remain high through late mitosis, after which they decline dramatically as cells begin the next cell cycle. We report that Dbf4p levels are sensitive to mutations in key components of the anaphase-promoting complex (APC). In addition, Dbf4p is modified in response to DNA damage, and this modification is dependent upon the DNA damage response pathway. We had previously shown that Dbf4p interacts with the M phase polo-like kinase Cdc5p, a key regulator of the APC late in mitosis. These results further link the actions of the initiator protein, Dbf4p, to the completion of mitosis and suggest possible roles for Dbf4p during progression through mitosis.

* Corresponding author. Mailing address: Department of Genetics, Washington University School of Medicine, Box 8232, 660 South Euclid Ave., St. Louis, MO 63110. Phone: (314) 747-1808. Fax: (314) 362-7855. E-mail: chardy{at}genetics.wustl.edu.

Molecular and Cellular Biology, June 1999, p. 4270-4278, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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