Fifty years after the replicon hypothesis: cell-specific master regulators as new players in chromosome replication control

Abstract

Numerous free-living bacteria undergo complex differentiation in response to unfavorable environmental conditions or as part of their natural cell cycle. Developmental programs require the de novo expression of several sets of genes responsible for morphological, physiological, and metabolic changes, such as spore/endospore formation, the generation of flagella, and the synthesis of antibiotics. Notably, the frequency of chromosomal replication initiation events must also be adjusted with respect to the developmental stage in order to ensure that each nascent cell receives a single copy of the chromosomal DNA. In this review, we focus on the master transcriptional factors, Spo0A, CtrA, and AdpA, which coordinate developmental program and which were recently demonstrated to control chromosome replication. We summarize the current state of knowledge on the role of these developmental regulators in synchronizing the replication with cell differentiation in Bacillus subtilis, Caulobacter crescentus, and Streptomyces coelicolor, respectively.

FIG 1

Chromosome distributions during the developmental life cycles of B. subtilis, S. coelicolor, and C. crescentus. Darker colors indicate intensive chromosomal replication or higher protein concentrations of the master regulators, Spo0A, AdpA, and CtrA.

FIG 2

Organization of the origin regions (oriC) from C. crescentus, B. subtilis, and S. coelicolor. Positions of the binding sites of master regulators CtrA, Spo0A, AdpA (red), and DnaA (black) are shown. Filled, stripped, empty, and dotted boxes (in that order) represent increasing deviations from the consensus sequence. Gray rectangles indicate AT-rich sequences; the oval DUE represents the DNA unwinding element; Ps represents the transcription start site from the strong hemE promoter. The DUE for C. crescentus and S. coelicolor origins has not been defined.

FIG 3

Master regulators coordinate the cell cycle with DNA replication. Examples of genes involved in cell cycle developmental processes and replication, which are regulated by Spo0A, CtrA, and AdpA proteins, respectively, are listed in boxes (for full lists of genes regulated by these transcription factors, see references , , , , and 118). The dotted line indicates an indirect multilevel interaction.