Molecular Microbiology
Molecular Microbiology
5 years ago

Genetic networks controlled by the bacterial replication initiator and transcription factor DnaA in Bacillus subtilis

Genetic networks controlled by the bacterial replication initiator and transcription factor DnaA in Bacillus subtilis
Alan D. Grossman, Tracy A. Washington, Janet L. Smith
DnaA is the widely conserved bacterial AAA+ ATPase that functions as both the replication initiator and a transcription factor. In many organisms, DnaA controls expression of its own gene and likely several others during growth and in response to replication stress. To evaluate the effects of DnaA on gene expression, separate from its role in replication initiation, we analyzed changes in mRNA levels in Bacillus subtilis cells with and without dnaA, using engineered strains in which dnaA is not essential. We found that dnaA was required for many of the changes in gene expression in response to replication stress. We also found that dnaA indirectly affected expression of several regulons during growth, including those controlled by the transcription factors Spo0A, AbrB, PhoP, SinR, RemA, Rok and YvrH. These effects were largely mediated by the effects of DnaA on expression of sda. DnaA activates transcription of sda, and Sda inhibits histidine protein kinases required for activation of the transcription factor Spo0A. We also found that loss of dnaA caused a decrease in the development of genetic competence. Together, our results indicate that DnaA plays an important role in modulating cell physiology, separate from its role in replication initiation. DnaA functions as both the replication initiator and a transcription factor. We used strains that tolerate null mutations in dnaA and found that dnaA affects expression of many genes, a handful directly and most indirectly. Many of the genes affected by DnaA were through its direct effect on transcription of the checkpoint gene sda, and subsequent effects of Sda on activity and expression of other transcription factors, including Spo0A.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/mmi.13755

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