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Molecular and Cellular Biology, January 2000, p. 242-248, Vol. 20, No. 1
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Dbf4p, an Essential S Phase-Promoting Factor, Is Targeted for Degradation by the Anaphase-Promoting Complex

Miguel Godinho Ferreira, Corrado Santocanale, Lucy S. Drury, and John F. X. Diffley*

ICRF Clare Hall Laboratories, South Mimms EN6 3LD, United Kingdom

Received 8 February 1999/Returned for modification 8 July 1999/Accepted 1 October 1999

The Dbf4p/Cdc7p protein kinase is essential for the activation of replication origins during S phase. The catalytic subunit, Cdc7p, is present at constant levels throughout the cell cycle. In contrast, we show here that the levels of the regulatory subunit, Dbf4p, oscillate during the cell cycle. Dbf4p is absent from cells during G1 and accumulates during the S and G2 phases. Dbf4p is rapidly degraded at the time of chromosome segregation and remains highly unstable during pre-Start G1 phase. The rapid degradation of Dbf4p during G1 requires a functional anaphase-promoting complex (APC). Mutation of a sequence in the N terminus of Dbf4p which resembles the cyclin destruction box eliminates this APC-dependent degradation of Dbf4p. We suggest that the coupling of Dbf4p degradation to chromosome separation may play a redundant role in ensuring that prereplicative complexes, which assemble after chromosome segregation, do not immediately refire.

* Corresponding author. Mailing address: ICRF Clare Hall Laboratories, South Mimms, Herts. EN6 3LD, United Kingdom. Phone: 44-171-269-3869. Fax: 44-171-269-3801. E-mail: J.Diffley{at}icrf.icnet.uk.

Molecular and Cellular Biology, January 2000, p. 242-248, Vol. 20, No. 1
0270-7306/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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