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GENES & DEVELOPMENT 19:2295-2300, 2005
©2005 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH COMMUNICATION

Cdc7–Drf1 is a developmentally regulated protein kinase required for the initiation of vertebrate DNA replication

Tatsuro S. Takahashi and Johannes C. Walter1

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA

Cdc7, a protein kinase required for the initiation of eukaryotic DNA replication, is activated by a regulatory subunit, Dbf4. A second activator of Cdc7 called Drf1 exists in vertebrates, but its function is unknown. Here, we report that in Xenopus egg extracts, Cdc7-Drf1 is far more abundant than Cdc7-Dbf4, and removal of Drf1 but not Dbf4 severely inhibits phosphorylation of Mcm4 and DNA replication. After gastrulation, when the cell cycle acquires somatic characteristics, Drf1 levels decline sharply and Cdc7-Dbf4 becomes the more abundant kinase. These results identify Drf1 as a developmentally regulated, essential activator of Cdc7 in Xenopus.

[Keywords: Cdc7; Drf1; Dbf4; DNA replication; Xenopus; developmental regulation]

Received June 2, 2005; revised version accepted August 3, 2005.

Supplemental material is available at http://www.genesdev.org.

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1339805.

1 Corresponding author.

E-MAIL johannes_walter{at}hms.harvard.edu; FAX (617) 738-0516.


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