Fifty Years after the Replicon Hypothesis: Cell-Specific Master Regulators as New Players in Chromosome Replication Control

Abstract

bNumerous 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.

oriC-encoded instructions for the initiation of bacterial chromosome replication

“…In bacteria that undergo a complex life cycle (e.g., Bacillus, Caulobacter , and Streptomyces ), the regulation of replication initiation must also be adjusted to the developmental stage to ensure that each nascent cell receives a single copy of the chromosome (Wolański et al, 2014 ). Recently, master transcription factors known to regulate the expression levels of hundreds of genes involved in cell cycle progression and cell differentiation were demonstrated to be also involved in controlling frequency of chromosomal replication initiation events.…”

“…Examples of these are Spo0A, CtrA, and AdpA proteins, which temporally and spatially coordinate chromosome replication with developmental program in B. subtilis, C. crescentus , and S. coelicolor , respectively (Laub et al, 2000 , 2002 ; Molle et al, 2003 ; Fujita and Losick, 2005 ; Fujita et al, 2005 ; Ohnishi et al, 2005 ; Wolański et al, 2011 ). They bind specifically to relevant recognition sequences within the origin of replication and inhibit the binding of DnaA, thereby disrupting assembly of the DnaA oligomer and inhibiting replication initiation (Siam and Marczynski, 2000 ; Castilla-Llorente et al, 2006 ; Taylor et al, 2011 ; Wolański et al, 2012 ; Boonstra et al, 2013 ; reviewed in Wolański et al, 2014 ). In all three cases, the binding sites for these regulators overlap with one or more DnaA binding sites, setting up a competition between the regulator and initiator for binding to oriC (Figure 2 ).…”

The Caulobacter crescentus Homolog of DnaA (HdaA) Also Regulates the Proteolysis of the Replication Initiator Protein DnaA

“…hile most bacteria use the DnaA protein to initiate chromosome replication (1)(2)(3), bacteria responding to diverse environmental pressures probably evolved many different mechanisms to regulate DnaA and thereby adjust replication control to their specific needs (3)(4)(5). The model Gram-negative bacterium Caulobacter crescentus is found in nutrient-poor freshwater lakes and streams (6).…”

Trends in symbiont-induced host cellular differentiation

“…By binding to the DNA promoters and regulatory regions made accessible by epigenetic modifications, transcription factors are also very important to cellular differentiation. This is true for both eukaryotes as well as bacteria, which use transcription factors to differentiate into different metabolic or motility states in response to environmental signals (Laub et al 2007;Cole and Young 2008;Losick and Desplan 2008;Wolański et al 2014).…”