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  • Book
    Sharon Elizabeth Hoover.
    Cells of Bacillus subtilis monitor the status of the chromosome to coordinate the initiation of sporulation with DNA replication and repair. When DNA replication is perturbed, transcription of the gene encoding the replication checkpoint protein -- Sda -- is induced, inhibiting sporulation-specific gene expression. Although the regulation of sda by replication stress has previously been studied using transient and chronic blocks to DNA replication factors as well as DNA damaging agents, other kinds of environmental conditions or changes in metabolism might also perturb DNA replication and thus inhibit sporulation. We performed a genetic screen to look for mutations that activate the sda checkpoint and found that many mutations in central metabolism caused a replication stress that activated Sda expression. We have been characterizing two examples in which the Sda checkpoint is active. In the first example, cells lacking the TCA cycle enzyme citB, encoding aconitase, are defective for initiation of sporulation. In the second example, cells grown into stationary phase in the nutrient rich medium LB do not sporulate unless supplemented with additional manganese. As B. subtilis cells enter into stationary phase in the absence of aconitase or when manganese levels are low, the Sda checkpoint prevents cells from initiating sporulation. Since the Sda checkpoint inhibits the initiation of sporulation when the cells are experiencing problems with DNA replication, these data suggest that Sda prevents cells from sporulating when manganese is limited or in aconitase deficient cells because they are encountering difficulties replicating their DNA and hint that the range of situations under which cells are experiencing such stresses is broader than initially anticipated.