The elucidation of the regulation mechanism of DNA replicaion is extremely important not only because cell division is under the direct control of DNA replication but also because the mechanism, as such, appears to be unique in biochemical regulatory systems. It has been known that the initiation of a round of DNA replication involves a mechanism which requires protein and RNA synthesis. Evidence suggests that there is another mechanism to inactivate the initiation ability in each cycle of DNA replication and that this inactivation activity is associated with the DNA replication complex. The long range goal of this proposal is to define the elements which are involved in the inactivation mechanism. It is proposed in this project to isolate Escherichia coli mutants that have alterations in the mechanism and to characterize them both genetically and biochemically.