Spo0A, the key transcriptional regulator for entrance into sporulation, is an inhibitor of DNA replication

The transcription factor Spo0A is a master regulator for entry into sporulation in Bacillus subtilis and also regulates expression of the virulent B. subtilis phage phi 29. Here, we describe a novel function for Spo0A, being an inhibitor of DNA replication of both, the phi 29 genome and the B. subtilis chromosome. Binding of Spo0A near the phi 29 DNA ends, constituting the two origins of replication of the linear phi 29 genome, prevents formation of phi 29 protein p6-nucleoprotein initiation complex resulting in inhibition of phi 29 DNA replication. At the B. subtilis oriC, binding of Spo0A to specific sequences, which mostly coincide with DnaA-binding sites, prevents open complex formation. Thus, by binding to the origins of replication, Spo0A prevents the initiation step of DNA replication of either genome. The implications of this novel role of Spo0A for phage phi 29 development and the bacterial chromosome replication during the onset of sporulation are discussed.