Dbf4p, an essential S phase-promoting factor, is targeted for degradation by the anaphase-promoting complex

The Dbf4p/Cdc7p protein kinase is essential for the activation of replicati on origins during S phase. The catalytic subunit, Cdc7p, is present at cons tant levels throughout the cell cycle. In contrast, we show here that the l evels of the regulatory subunit, Dbf4p, oscillate during the cell cycle. Db f4p is absent from cells during G(1) and accumulates during the S and G(2) phases. Dbf4p is rapidly degraded at the time of chromosome segregation and remains highly unstable during pre-Start G(1) phase. The rapid degradation of Dbf4p during G(1) requires a functional anaphase-promoting complex (APC ), Mutation of a sequence in the N terminus of Dbf4p which resembles the cy clin destruction box eliminates this APC-dependent degradation of Dbf4p. We suggest that the coupling of Dbf4p degradation to chromosome separation ma y play a redundant role in ensuring that prereplicative complexes, which as semble after chromosome segregation, do not immediately refire.