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

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Abstract
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 ϕ29. Here, we describe a novel function for Spo0A, being an inhibitor of DNA replication of both, the ϕ29 genome and the B. subtilis chromosome. Binding of Spo0A near the ϕ29 DNA ends, constituting the two origins of replication of the linear ϕ29 genome, prevents formation of ϕ29 protein p6‐nucleoprotein initiation complex resulting in inhibition of ϕ29 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 ϕ29 development and the bacterial chromosome replication during the onset of sporulation are discussed.