Download Regulation of the initiation of chromosomal replication in bacteria

Regulation of the initiation of chromosomal replication in bacteria
Jolanta Zakrzewska-Czerwińska1, Dagmara Jakimowicz1, Anna Zawilak-Pawlik1 & Walter Messer2
1
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland; and 2Max Planck Institute for Molecular
Genetics, Berlin, Germany
Correspondence: Jolanta ZakrzewskCzerwińska, Ludwik Hirszfeld Institute of
Immunology and Experimental Therapy,
Polish Academy of Sciences, ul. Weigla 12,
53-114, Wrocław, Poland. Tel.: 148 71
3709948; fax: 148 71 3371382; e-mail:
[email protected]
Received 31 October 2006; revised 28 February
2007; accepted 1 March 2007.
First published online 25 April 2007.
DOI:10.1111/j.1574-6976.2007.00070.x
Abstract
The initiation of chromosomal replication occurs only once during the cell cycle
in both prokaryotes and eukaryotes. Initiation of chromosome replication is the
first and tightly controlled step of a DNA synthesis. Bacterial chromosome
replication is initiated at a single origin, oriC, by the initiator protein DnaA, which
specifically interacts with 9-bp nonpalindromic sequences (DnaA boxes) at oriC.
In Escherichia coli, a model organism used to study the mechanism of DNA
replication and its regulation, the control of initiation relies on a reduction of the
availability and/or activity of the two key elements, DnaA and the oriC region. This
review summarizes recent research into the regulatory mechanisms of the initiation of chromosomal replication in bacteria, with emphasis on organisms other
than E. coli.
Editor: Rafael Giraldo
Keywords
DnaA; oriC ; orisome; regulatory protein;
two-component signal-transduction system.
Introduction
The events involved in the initiation of chromosomal
replication are similar in Eubacteria, eukaryotes, and Archea: replication starts with the binding of specific initiator
protein(s) to DNA sites, termed origins, and results in the
localized unwinding of the DNA duplex and the establishment of replication forks. In eukaryotes, chromosomes
contain multiple start sites for DNA synthesis, and the
initiator origin recognition complex (ORC) is a six-subunit
heteromultimer that binds to the origin region. In contrast,
bacteria replicate their chromosome(s) from a single replication origin (oriC), and the initiation of chromosome
replication is mediated by a single initiator protein, DnaA,
which specifically interacts with 9-bp nonpalindromic sequences (DnaA boxes) at oriC (Messer, 2002; Kaguni, 2006).
This process has been particularly well characterized in
Escherichia coli. Twenty to 30 DnaA monomers interact with
11 binding sites. Three of these sites are high-affinity
binding sites; the others [two 9-mer DnaA boxes, three
6-mer DnaA–ATP boxes (Weigel et al., 1997; Speck & Messer,
2001) and three 9-mer I sites (Leonard & Grimwade, 2005)]
require oligomerization of DnaA. Erzberger et al. (2002,
2006) proposed a model of DnaA oligomerization at oriC
based on the recently resolved crystal structure of the major
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part of Aquifex aeolicus DnaA (domains III and IV). In this
model, DnaA monomers bound to DnaA boxes together
with DnaA monomers oligomerize into right-handed filament; a newly created nucleoprotein complex is stabilized by
specific protein–ATP interactions of adjacent DnaA monomers. Additional stability may be provided by domain I,
which is responsible for self-oligomerization (Weigel et al.,
1999; Felczak et al., 2005). Wrapping of the oriC region
around the DnaA filament promotes a local unwinding of an
AT-rich region that leads to the formation of the open
complex. Because there are flexible links between the
respective DnaA domains responsible for oligomerization,
ATP binding, and DNA binding, it is easy to imagine how
the origins of other bacteria with different numbers and
orientations of DnaA boxes adjust to their cognate DnaA
proteins (Zawilak-Pawlik et al., 2005). As a result of
DnaA–DnaB and DnaC–ssDNA interactions, the DnaB/
DnaC helicase complex is loaded into the unwound origin
region (Konieczny, 2003), and then DnaB loads DnaG
(Lu et al., 1996; Tougu & Marians, 1996) and DNA
polymerase III (Kim et al., 1996). The overall architecture
of the eukaryotic ORC is very similar to that of DnaA
oligomers (Clarey et al., 2006). This and the importance of
ATP binding for ORC–origin interaction exemplify the
global similarity of these basic processes. By analogy to
FEMS Microbiol Rev 31 (2007) 378–387
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Replication regulation
the DNA-wrapping activity of DnaA, ORC together with
Cdc6 prepares origins for helicase loading through mechanisms related to the established pathway of bacteria (Clarey
et al., 2006).
Replication initiation has to occur at the correct time in
the cell cycle, and any one origin must initiate once and only
once per cell cycle (Boye et al., 2000; Messer, 2002; Kaguni,
2006). In Eubacteria, eukaryotes, and, very likely, Archaea as
well, replication is controlled at the initiation stage (Maaloe
& Kjeldgaard, 1966). Various mechanisms are involved in
the regulation of this process. In Eubacteria, the control of
initiation relies on a reduction of the availability and/or
activity of both the DnaA protein and the oriC region at the
various steps after initiation, for example before unwinding
and/or immediately after the establishment of replication
forks.
Regulatory mechanisms in E. coli -- a short
overview
The initiation of replication is controlled by affecting the
assembly of the orisomes (protein–oriC complexes). Recent
extensive studies have shown that the E. coli orisome
structure is dynamic, changing in stages as it progresses
through the cell cycle of this bacterium (Cassler et al., 1995;
Leonard & Grimwade, 2005; Schaeffer et al., 2005). In E. coli,
several orisome components have been identified, including
the histone-like DNA-binding proteins IHF and Fis, and
other oriC-binding elements such as HU, Dpi, IciA, Cnu,
Hha, Rob, SeqA, and ArcA (Kim et al., 2005). Orisome
assembly is regulated by a dynamic interplay among these
proteins; for example, Fis and IHF directly modulate the
interaction of DnaA–ATP with its weaker binding sites,
while HU modulates the binding of IHF to oriC and
presumably enhances the ability of DnaA to unwind the
origin (Hwang & Kornberg, 1992; Ryan et al., 2004). In
contrast to IHF, IciA inhibits the unwinding of oriC.
However, the contribution of IciA and other proteins, Dpi,
Cnu, Hha, and Rob, to orisome assembly or disassembly
during the cell cycle remains to be elucidated. The assembly
of orisomes could also be affected by proteins that directly
interact with DnaA. Recently, DiaA, a novel DnaA-binding
protein crucial to ensuring the timely initiation of replication, was identified in E. coli (Ishida et al., 2004).
Three key negative regulation mechanisms preventing
reinitiation from the newly replicated origins have been
described in E. coli: (1) inhibition of DnaA activity, (2)
titration of the free form of DnaA, and (3) sequestration of
the oriC. Inactivation of DnaA protein occurs by conversion
of the active initiator DnaA–ATP form to inactive
DnaA–ADP, which is stimulated by the replisome elements,
namely the DnaN sliding clamp of DNA polymerase III and
Hda protein, and is called RIDA (regulatory inactivation of
FEMS Microbiol Rev 31 (2007) 378–387
DnaA) (Katayama et al., 1998; Kato & Katayama, 2001; Gon
et al., 2006; Riber et al., 2006). A second mechanism
preventing reinitiation involves titration of DnaA protein
by a cluster of high-affinity DnaA boxes (named datA, DnaA
titration), which reduces the level of DnaA shortly after this
region is duplicated. The datA region is able to bind over 300
DnaA molecules (Kitagawa et al., 1998). In the third
regulatory mechanism, the newly replicated and therefore
hemimethylated oriC regions are sequestered by the binding
of SeqA protein. SeqA recognizes GATC sequences overrepresented within oriC and prefers binding to hemimethylated over binding to fully or unmethylated oriC.
These three mechanisms of E. coli have been discussed in
a number of excellent reviews (Boye et al., 2000; Katayama,
2001; Messer, 2002; Margolin & Bernander 2004; Camara
et al., 2005; Cunningham & Berger, 2005; Kato 2005;
Lobner-Olesen et al., 2005; Kaguni, 2006). Because much
of what is know about the regulation of the initiation of
bacterial chromosomal replication comes from studies of
E. coli, this review focuses mainly on regulatory mechanisms
in organisms other than E. coli (Fig. 1).
Escherichia coli -like mechanisms in other
organisms
The inactivation of DnaA–ATP by ATP hydrolysis is likely to
take place in all bacteria possessing a dnaA gene. Besides
being established for E. coli DnaA, ATPase activity has also
been demonstrated for other bacterial DnaA proteins,
including Bacillus subtilis (Fukuoka et al., 1990), Helicobacter pylori (A. Zawilak-Pawlik unpublished results), Mycobacterium tuberculosis (Yamamoto et al., 2002; Madiraju et al.,
2006), Streptomyces coelicolor (Majka et al., 1997), Thermus
thermophilus (Schaper et al., 2000), and Thermotoga maritima (Ozaki et al., 2006). So far, all sequenced dnaA genes
encode an AAA1ATPase motif responsible for the binding
and hydrolysis of ATP. Furthermore, this motif is also
present in proteins that initiate chromosome replication in
eukaryotes (three ORC proteins, namely Orc1p, Orc4p and
Orc5p, and Cdc6) (Speck et al., 2005) and Archaea (Cdc6/
Orc1) (Robinson & Bell, 2005). All these proteins are
replication-active in the ATP-bound form (Lee and Bell
2000; Davey et al., 2002). Thus, ATP binding and hydrolysis
acts as a universal switch that regulates the initiation of
replication in three domains of life. Little is known about the
mechanism(s) responsible for the inactivation of the ATPbound form of initiators. It should be noted that orthologues of Hda are present only in certain gammaproteobacterial genomes, suggesting the presence of different regulation
systems in the replication initiation process of Eubacteria.
Titration of the DnaA protein by a cluster of high-affinity
DnaA boxes localized outside oriC also appears to be
involved in the regulation of chromosome replication in
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380
J. Zakrzewska-Czerwińska et al.
DnaA-ADP
DnaA proteolysis
Cc
transcription
regulation
Bs, Cc, Ec, Sc?
regeneration
RIDA
all bacteria?
DnaA modulating proteins
Hp - Hp1230
Ec - DiaA
Bs - DnaB, DnaD, YabA
titration
Ec, Bs?, Sc
initiation
DnaA-ATP
Clusters of DnaA boxes
dnaA
oriC
genes involved in replication
regulators
Mt - MtrA~P
- promoter region
acessory
methylation
elements
Ec - Dam methylation,
SeqA sequestration Ec - Fis, IHF,
HU, Hha,
Cc - CcrM methylation
Rob,Cnu,
Dpi, IciA
Cc - IHF
Bs - B. subtilis
Cc - C. crescentus
Ec - E. coli
RIDA - regulatory inactivation of DnaA (Hda, DnaN in E. coli )
regulators - two-component regulatory system
regeneration - acidic phospholipids
regulators
Ec - ArcA~P
Cc - CtrA~P
Bs - Spo0A~P
Mt - M. tuberculosis
Hp - H. pylori
Sc - S. coelicolor
Fig. 1. Regulatory mechanisms of the initiation of bacterial chromosome replication.
other bacteria. The S. coelicolor chromosome contains a
cluster of high-affinity DnaA boxes in the vicinity of the
oriC region (Smulczyk-Krawczyszyn et al., 2006). Deletion
of the cluster caused more frequent chromosome replication
and led to earlier colony maturation. In contrast, delivery of
high-affinity DnaA boxes caused slow colony growth, presumably because of a reduction in the frequency of replication initiation. In silico analysis of bacterial chromosomes
revealed that many of them contain at least two clusters of
DnaA boxes in the vicinity of the oriC region (Mackiewicz
et al., 2004). Thus the presence of additional clusters of
DnaA boxes in chromosomes other than those of E. coli or
S. coelicolor suggests that such control may be a common
mechanism for many bacteria.
Up until now, sequestration of the oriC region has seemed
to be a mechanism exclusively characteristic of E. coli and
other enterobacteria. However, some recent data suggest
that the initiation of replication of Agrobacterium tumefaciens (Kahng & Shapiro, 2001), Brucella abortus, Caulobacter
crescentus (Stephens et al., 1995), Rhizobium meliloti, and
Rickettsia prowazekii, and probably of other organisms from
a-subdivision bacteria, might involve an analogous system;
these organisms possess a cell cycle-regulated CcrM DNA
methyltransferase that recognizes the GANTC sequence
(Stephens et al., 1996). Interestingly, in some bacteria that
do not have the sequestration mechanism, such as B. subtilis
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and Streptomyces, minichromosomes are unstable, and only
low copy numbers occur; in contrast to E. coli, minichromosomes of these organisms compete with chromosomes
(Zakrzewska-Czerwińska & Schrempf, 1992; Moriya et al.,
1999; Paulsson & Chattoraj, 2006; Smulczyk-Krawczyszyn
et al., 2006). From studies on these bacteria, it is becoming
clear that their chromosomal replication control shares
some similarities with that of low-copy-number plasmids,
such as miniP1. In both cases, DnaA boxes or plasmid
iterons (binding sites for initiator protein) serve as incompatibility elements (Mukhopadhyay & Chattoraj, 2000,
Ogura et al., 2001, Park et al., 2001). Perhaps handcuffing
(origin pairing causing steric hindrance) may also apply to
B. subtilis and Streptomyces replication control.
As in E. coli, the assembly of orisomes in other bacteria is
affected by proteins that interact with oriC and/or DnaA. In
C. crescentus, IHF and CtrA (see below) bind the oriC region
specifically. Bacillus subtilis lacks genes encoding proteins
homologous to E. coli accessory proteins, IHF, Hha, Fis,
SeqA, Dam, but several novel proteins modulating orisome
assembly have been identified in B. subtilis, including
Spo0A, an oriC-binding protein (see below), DnaD and
DnaB, which participate in loading the DnaC–DnaI helicase
complex (equivalent to E. coli DnaBC) at oriC (Bruand et al.,
2005; Zhang et al., 2005, 2006; Carneiro et al., 2006), and
YabA, interacting with DnaA and DnaN (Noirot-Gros
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Replication regulation
et al., 2002, 2006; Hayashi et al., 2005). However, their exact
biological function in B. subtilis orisome assembly is not yet
fully understood. Recently, in H. pylori a novel, essential
architectural component of the orisome, HobA, was found
(A. Zawilak-Pawlik unpublished results).
In E. coli, DnaA protein, besides being the initiator, is also
a transcription factor regulating the expression of genes that
are involved in replication (e.g. mioC, nrd), including its
own gene; binding of the DnaA protein to DnaA boxes
located within promoter regions influences gene expression
(Messer & Weigel, 1997). The DnaA protein also regulates
gene expression in B. subtilis (Goranov et al., 2005), C.
crescentus (Hottes et al., 2005), and, presumably, in other
organisms whose promoter regions contain DnaA-binding
motifs.
Free-living bacteria
A global network relevant to regulating replication is likely
to be more intricate in organisms that undergo a complex
life cycle or in those that have to adapt to highly fluctuating
environmental conditions. Under unfavourable conditions,
the growth rate should be reduced and/or the bacteria
should undergo morphological changes. In these organisms
the decision ‘to replicate or not to replicate’ has to be
precisely controlled at a number of levels. Bacteria, much
like eukaryotic cells, coordinate cell division with DNA
replication. Little is known about how the replication
machinery coordinates its action with other cellular processes in variable environmental conditions. Adaptation in
bacterial cells is often achieved through two-component
signal-transduction systems, which consist of a sensor
kinase and a response regulator. So far, only a few bacterial
two-component signal-transduction systems involved in
the regulation of replication initiation have been described.
One of them is E. coli Arc (anoxic redox control), a twocomponent signal-transduction system that participates in
regulating chromosomal initiation under anaerobic growth
conditions (Iuchi & Weiner, 1996). The Arc system regulates
the expression of numerous operons in response to respiratory growth conditions. It consists of the ArcB, a transmembrane sensor kinase, and its cognate response regulator,
ArcA. Anaerobic conditions that induce the Arc two-component signal-transduction system lead to a reduction in the
growth rate. Lee et al. (2001) demonstrated in vitro that
ArcAP specifically binds the left part of the E. coli oriC
region and prevents the formation of the open complex.
Thus, oxygen depletion stress promotes the conversion of
ArcA to ArcAP and its binding to oriC, which consequently reduces the frequency of chromosomal initiation to
sustain a slow growth rate in adverse environmental conditions. Similarly, PhoB protein, a transcriptional regulator of
the PhoB–PhoR two-component system regulating phosFEMS Microbiol Rev 31 (2007) 378–387
phate uptake, affects E. coli chromosome initiation.
PhoBP, under reduced phosphate availability, activates
iciA transcription (Han et al., 1999). IciA is a negative
regulator of oriC unwinding in vitro; hence PhoBP might
reduce the initiation frequency during phosphate starvation.
Switching off replication by preventing a new round of
replication must also occur at certain stages of the life cycles
of bacteria that undergo cellular differentiation, for example
the formation of morphologically different cells (C. crescentus) and/or the production of endospores or exospores
(B. subtilis or S. coelicolor). An interesting example of a
response regulator of the two-component system involved
in the regulation of the cell cycle, including inhibition of
chromosome replication, is CtrA (cell-cycle transcription
regulator) in C. crescentus (McAdams & Shapiro, 2003;
McGrath et al., 2004). This is a free-living bacterium in an
aquatic environment that divides asymmetrically, generating
two distinct cell types at each cell division: a stalked cell
competent for DNA replication and a swarmer cell that is
unable to initiate DNA replication until it differentiates into
a stalked cell later in the cell cycle (Crosson et al., 2004;
Brazhnik & Tyson, 2006; Holtzendorff et al., 2006; Jensen,
2006). In swarmer cells, CtrAP binds specifically to five
sites located within the oriC region, preventing the formation of the replisome (Quon et al., 1998; Siam & Marczynski,
2000; Wortinger et al., 2000; Marczynski & Shapiro, 2002).
At the swarmer-to-stalked cell transition, CtrA is temporally
degraded by the ClpXP protease, which releases the origin
for replication initiation (Jenal & Fuchs, 1998). Shortly after
replication initiation, the proteolysis of CtrA is stopped and
a positive transcriptional feedback loop results in the
accumulation of new CtrA protein (Domain et al., 1999;
Hung & Shapiro, 2002), thus preventing premature reinitiation of DNA replication (Quon et al., 1998). In C. crescentus,
DnaA protein is also selectively targeted for proteolysis, but
DnaA proteolysis uses a different mechanism from that of
CtrA (Gorbatyuk & Marczynski, 2005). Unlike the case for
E. coli DnaA, the degradation of C. crescenus DnaA depends
on cell-cycle- and nutrition-specific signalling; it takes place
preferentially in swarmer cells. In C. crescentus, both proteins, DnaA and CtrA, regulate the transcriptions of multiple genes: DnaA controls the expression of genes encoding
several replisome components, and CtrA controls the expression of many genes involved in flagella biogenesis and
cell division. In addition to CtrA, a second master regulatory
protein, GcrA, is involved in the cell-cycle regulation of
C. crescentus (Holtzendorff et al., 2006). GcrA is present
predominantly in stalked cells. GcrA also affects the expression of many genes: it inhibits dnaA expression and activates
genes encoding components of the segregation machinery
and the ctrA gene (p1 promoter) (Holtzendorff et al., 2004).
Its expression is inhibited by CtrA and activated by DnaA
protein (Collier et al., 2006).
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382
At certain stages of life, usually in response to nutritional
stress, bacteria can form dormant, nonreproductive bodies
(e.g. spores). The formation of such temporarily inactive
cells has to be preceded by the completion of a final
replication round and by the prevention of a new round of
replication at the initiation step. During sporulation of
B. subtilis, a single cell divides asymmetrically (in contrast
to vegetative growth) near one pole, producing a small
endospore and a large mother cell that participates in the
maturation of the spore and finally lyses to release it. In B.
subtilis, Spo0A is a key transcriptional regulator controlling
the entrance into sporulation. Spo0A belongs to a superfamily of phosphorylation-activated signal-transduction
proteins that mediate adaptive responses to environmental
or metabolic signals (Baldus et al., 1994; Burkholder et al.,
2001) and activate the transcription of crucial genes for the
sporulation process. It has recently been demonstrated that
Spo0A is involved in the regulation of replication frequency.
In addition to being required for the onset of sporulation,
Spo0A is a transcriptional activator/repressor that influences the expression of over 500 genes. Spo0A binds to socalled ‘0A-boxes’, which have been found not only within the
promoter regions, but also within the B. subtilis oriC region,
suggesting a novel function for the protein. Indeed, CastillaLiorente et al. (2006) showed that binding of Spo0A protein
to ‘0A-boxes’, which overlap with functional DnaA-binding
sites of the oriC region, prevents open complex formation.
Recent advances in bacterial cell biology have revealed
that the nucleoid is a highly organized structure that undergoes dynamic changes through the cell cycle, for example
during segregation (Errington et al., 2005). Chromosomal
regions are organized into highly ordered structures that are
placed in discrete spatial locations at specific times. It has
been suggested that, in B. subtilis, Soj and Spo0J proteins
(ParA and ParB homologues) required for chromosome
segregation may be the negative regulator of replication
initiation. In vivo, Spo0J binds to eight parS sites distributed
around oriC (Lee et al., 2003; Murray et al., 2006). The
formation of a massive nucleoprotein complex that compacts the oriC region presumably prevents reinitiation from
the newly replicated origins by reducing origin accessibility
for the initiator protein DnaA (Lee & Grossman, 2006).
Indeed, deletion of soj and spo0J causes overinitiation of
replication in B. subtilis (Lee & Grossman, 2006).
Similarly, in Streptomyces, ParB, besides being the protein
involved in segregation, may also regulate the initiation of
replication. Streptomyces, which are known for their ability
to produce many valuable antibiotics, are among the most
striking examples of multicellular bacteria. Their hyphae
grow by tip extension, forming a branched vegetative
mycelium that consists of hyphal compartments containing
multiple chromosomes; thus cross-wall formation is uncoupled from chromosome replication and segregation.
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J. Zakrzewska-Czerwińska et al.
During further growth, Streptomyces colonies form an aerial
mycelium that develops into long chains of uninucleoidal
exospores. At this stage, intensive replication in rapidly
growing compartments is subsequently switched off as the
chromosomes become condensed and segregated into
spores. As in B. subtilis, it was shown that ParB is engaged,
particularly during sporulation, in the formation of
large nucleoprotein complexes encompassing oriC regions
(twenty parS sequences are clustered around the origin)
(Jakimowicz et al., 2002, 2005). It has been postulated that
compaction of the oriC region by ParB may prevent further
rounds of replication.
Intracellular pathogens and
endosymbionts
Little is known about the signalling pathways that link the
facultative intracellular cell cycle of pathogens with the host
environment. It has recently been shown that in M. tuberculosis the initiation of chromosome replication is regulated by
the signal-transduction system MtrA–MtrB, which is activated by specific host–pathogen interactions. The M. tuberculosis MtrA response regulator affects chromosome
replication in a phosphorylation-dependent manner by
inducing M. tuberculosis dnaA expression. The dnaA promoter is a MtrA target, as confirmed by immunoprecipitation experiments using anti-MtrA antibodies (Fol et al.,
2006). Elevating the intracellular levels of MtrA has no effect
on bacterial growth in broth, while it prevents the proliferation of M. tuberculosis in macrophages and in mice lungs
and spleens. In human macrophage cell lines, the transcript
levels of dnaA were significantly increased (c. 40-fold) in an
mtrA overexpression strain relative to the wild type. Furthermore, the same phenotypes were observed when dnaA
expression was artificially induced (dnaA was under the
control of an inducible promoter), which suggests that
the overexpression of DnaA inhibits the proliferation of
M. tuberculosis (Hoskisson & Hutchings, 2006). Fol et al.
(2006) proposed that the proliferation of M. tuberculosis
in vivo depends, in part, on the optimal ratio of phosphorylated to nonphosphorylated MtrA response regulator.
Obligatory intracellular parasites and endosymbionts
existing continuously within the host or extremophiles
living under extreme conditions (e.g. high temperature) do
not experience the extreme environmental fluctuations
encountered by free-living bacteria (Moran, 2002). Sequence analysis of their chromosomes has demonstrated
that they have lost many genes and regulatory elements,
including those involved in the regulation of replication
initiation in free-living organisms.
In contrast to the case for pathogens, the proliferation of
obligatory endosymbionts has to be beneficial for the host.
Thus these organisms needed to adapt their replication in a
FEMS Microbiol Rev 31 (2007) 378–387
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Replication regulation
balanced way so that their growth rates were coordinated
with the development of their hosts. The development of a
stable symbiosis with cytosolic bacteria might have required
a more direct control of DNA replication of the symbionts
by the host (Gil et al., 2003). In extreme cases, some
obligatory insect endosymbionts, for example Wigglesworthia glossinidia (endosymbiont of the tsetse fly) (Akman
et al., 2002), Blochmannia floridanus (carpenter ant) (Gil
et al., 2003), Blochmannia pennsylvanicus (black carpenter
ant) (Degnan et al., 2005), and Baumannia cicadellinicola
(glassy-winged sharpshooter) (Wu et al., 2006), lost the
dnaA gene (Foster et al., 2005). The lack of DnaA protein
might allow the host to protect itself from overreplication of
the bacterium in its cytosol (Akman et al., 2002). It cannot
be excluded that other alternative replication initiation
pathways based on priA, priC or recA genes (Gil et al., 2003;
Wu et al., 2006) – commonly used in E. coli to re-establish
replication at damage sites – might be used in these
endosymbionts. Although Blochmannia also lacks priA, priC
and recA genes, it contains recBCD genes, which may play
some role in the initiation of replication (Wu et al., 2006).
Buchnera is an interesting endocellular bacterial symbiont of
aphids, which, in contrast to Wiggelsworthia and Blochmannia, retains the dnaA gene to initiate replication (in B.
aphidicola, only two DnaA boxes were identified within its
putative oriC region; Mackiewicz et al., 2004). However, it
should be noted that Buchnera resides in vacuole-like
organelles, while Wiggelsworthia and Blochmannia directly
contact the host cytoplasm.
Organisms that possess more than one
chromosome
Not all bacteria have a single chromosome: some bacteria
have multiple chromosomes; for example, Vibrio cholerae
possesses two chromosomes, while Burkholderia cepacia has
three chromosomes. The control of replication in bacteria
with multiple chromosomes is much less well understood
than that in organisms with a single chromosome. Among
the organisms possessing more than one chromosome, the
initiation of replication and the mechanism(s) regulating
this process have been studied so far only in V. cholerae. This
bacterium, the causative agent of cholera, has two differently
sized circular chromosomes, namely chromosome I (chrI)
and chromosome II (chrII), of 2.96 and 1.07 Mbp, respectively (Heidelberg et al., 2000). Vibrio cholerae lives primarily as a free organism in aquatic environments and associates
with the host only during short outbreaks. Egan & Waldor
(2003) suggested that a bipartite genomic arrangement may
provide an evolutionary advantage by facilitating a faster
replication time or by allowing chromosome-specific replication control in certain environments. However, so far,
none of these hypotheses has been experimentally proven.
FEMS Microbiol Rev 31 (2007) 378–387
Although the two chromosomes replicate synchronously,
they exhibit distinct replication requirements (Egan &
Waldor, 2003; Egan et al., 2004, 2005; Duigou et al., 2006).
The structure of oriCI resembles that of E. coli oriC, whereas
oriCII shares some features with certain plasmid replicons.
The functional oriCII requires internal 12-bp repeats and
two hypothetical genes that flank the origin. One of these
genes encodes the protein RctB that specifically binds oriCII.
DnaA and RctB independently control replication initiation
of the two chromosomes chrI and chrII, respectively. Overproduction of DnaA or RctB protein promoted exclusively
overinitiation of chromosome I or chromosome II, respectively. The distinct replication requirements of the two
origins may minimize competition between chromosomes,
ensuring the maintenance of the divided genome, but, on
the other hand, raise the question of how the regulation of
replication initiation of two chromosomes is coordinated.
Although oriCII has very little sequence similarity to oriCI, it
contains a single DnaA box and an overrepresentation of
GATC sequences, targets for the Dam methyltransferase.
Although DnaA protein does not initiate replication of the
chromosome II, its minimum concentration is required for
the initiation of chromosome II replication. A similar
situation is observed in the case of the replication of certain
plasmids, including RK2, where DnaA is known to promote
their replication, although they encode their own initiators,
such as TrfA (Duigou et al., 2006). The overrepresentation of
methylation motifs in both origins, oriCI and oriCII, of V.
cholerae and the presence of seqA and dam genes suggest that
these factors may mediate the coordination of replication of
two chromosomes in a similar manner to sequestration of
the E. coli origin. Additional, so far unknown, elements
probably coordinate the activity of both initiators, DnaA
and RctB.
Streptomyces and Rhizobium belong to the intriguing
group of bacteria whose cells are multinucleoidal at certain
stage(s) of the cell cycle. Thus these bacteria do not obey the
once-and-only-once doctrine of DNA replication at particular life stages. This characteristic feature raises interesting
questions on how the replication of multiple chromosomes
within a single cell/compartment is regulated. Very little is
known about the synchronization and regulation of chromosome replication in the multinucleoidal compartments
of Streptomyces. Recent data show that chromosome replication appears to be asynchronous within a single compartment; only selected chromosomes undergo replication at
one time (Ruban-Osmialowska et al., 2006). Rhizobium
endosymbiotic soil bacteria can incite root nodule formation in certain leguminous plants. After infection of plant
cells, the free-living bacteria are converted into nitrogenfixing bacteroids. The transformation includes an elongation of the cells and repeated chromosome replication
(endoreduplication) without cytokinesis, leading to the
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384
multinucleate cells. It has been demonstrated that plant
factors present in the nodules trigger endoreduplication
(Mergaert et al., 2006).
So far, Rhizobium and M. tuberculosis are the only two
examples for host cells–plant cells and human macrophages,
respectively – capable of triggering bacterial replication
frequency.
Concluding remarks
Much of what we know about the molecular mechanisms of
the regulation of bacterial chromosome replication comes
from studies of E. coli. So far, not many factors involved in
the regulatory network of the replication of organisms other
than E. coli have been identified. However, those identified
have demonstrated that the diversity in the mechanisms
involved in the regulation of replication initiation results
from the different life cycles and lifestyles of the microorganisms. Comparative analysis of bacterial genomes together with expression profiles of their genes under different
conditions and the application of high-throughput twohybrid systems (E. coli or yeast) for searching interacting
proteins will allow us to identify new regulatory mechanisms in the near future. The elements involved in the novel
mechanisms may provide valuable drug and vaccine targets
against bacterial pathogens.
Acknowledgements
This work was supported by the Ministry of Science and
Higher Education (grant 2P04A 054 29). D.J. acknowledges
support from the Marie Curie Reintegration Grant MERG6-CT-2005-014851. A. Z.-P. was supported by a Marie Curie
Intra-European Fellowship within the 6th European Community Framework Programme. J.Z.-C., A.Z.-P. and D.J.
acknowledge support from the Scientific and Technological
International Cooperation Joint Project Polonium.
References
Akman L, Yamashita A, Watanabe H, Oshima K, Shiba T, Hattori
M & Aksoy S (2002) Genome sequence of the endocellular
obligate symbiont of tsetse flies, Wigglesworthia glossinidia.
Nat Genet 32: 402–407.
Baldus JM, Green BD, Youngman P & Moran CP Jr (1994)
Phosphorylation of Bacillus subtilis transcription factor Spo0A
stimulates transcription from the spoIIG promoter by
enhancing binding to weak 0A boxes. J Bacteriol 176: 296–306.
Boye E, Lobner-Olesen A & Skarstad K (2000) Limiting DNA
replication to once & only once. EMBO Rep 1: 479–483.
Brazhnik P & Tyson JJ (2006) Cell cycle control in bacteria and
yeast: a case of convergent evolution? Cell Cycle 5: 522–529.
Bruand C, Velten M, McGovern S, Marsin S, Serena C, Ehrlich D
& Polard P (2005) Functional interplay between the Bacillus
2007 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
c
J. Zakrzewska-Czerwińska et al.
subtilis DnaD and DnaB proteins essential for initiation and
re-initiation of DNA replication. Mol Microbiol 55: 1138–1150.
Burkholder WF, Kurtser I & Grossman AD (2001) Replication
initiation proteins regulate a developmental checkpoint in
Bacillus subtilis. Cell 104: 269–279.
Camara JE, Breier AM, Brendler T, Austin S, Cozzarelli NR &
Crooke E (2005) Hda inactivation of DnaA is the predominant
mechanism preventing hyperinitiation of Escherichia coli DNA
replication. EMBO Reports 6: 1–6.
Carneiro MJV, Zhang W, Ioannou C, Scott DJ, Allen S, Roberts CJ
& Soultanas P (2006) The DNA-remodelling activity of DnaD
is the sum of oligomerization and DNA-binding activities on
separate domains. Mol Microbiol 60: 917–924.
Cassler MR, Grimwade JE & Leonard AC (1995) Cell cyclespecific changes in nucleoprotein complexes at a chromosomal
replication origin. EMBO J 14: 5833–5841.
Castilla-Liorente V, Munoz-Espin D, Villar L, Salas M & Meijer
WJJ (2006) Spo0A, the key transcriptional regulator for
entrance into sporulation, is an inhibitor of DNA replication.
EMBO J 25: 3890–3899.
Clarey MG, Erzberger JP, Grob P, Leschziner AE, Berger JM,
Nogales E & Botchan M (2006) Nucleotide-dependent
conformational changes in the DnaA-like core of the origin
recognition complex. Nat Struct Mol Biol 13: 684–690.
Collier J, Murray SR & Shapiro L (2006) DnaA couples DNA
replication and the expression of two cell cycle master
regulators. EMBO J 25: 346–356.
Crosson S, McAdams H & Shapiro L (2004) A genetic oscillator
and the regulation of cell cycle progression in Caulobacter
crescentus. Cell Cycle 10: 1252–1254.
Cunningham EL & Berger JM (2005) Unraveling the early steps of
prokaryotic replication. Curr Opin Struct Biol 15: 68–76.
Davey MJ, Jeruzalmi D, Kuriyan J & O’Donnell M (2002) Motors
and switches: AAA1machines within the replisome. Nat Rev
Mol Cell Biol 3: 826–835.
Degnan PH, Lazarus AB & Wernegreen JJ (2005) Genome
sequence of Blochmannia pennsylvanicus indicates parallel
evolutionary trends among bacterial mutualists of insects.
Genome Res 8: 1023–1033.
Domain IJ, Reisenauer A & Shapiro L (1999) Feedback control of
a master bacterial cell-cycle regulator. Proc Natl Acad Sci USA
96: 6648–6653.
Duigou S, Knudsen KG, Skovgaard O, Egan ES, Lbner-Olesen A
& Waldor MK (2006) Independent control of replication
initiation of the two Vibrio cholerae chromosomes by DnaA
and RctB. J Bacteriol 188: 6419–6424.
Egan ES, Fogel MA & Waldor MK (2005) Divided genomes:
negotiating the cell cycle in prokaryotes with multiple
chromosomes. Mol Microbiol 56: 1129–1138.
Egan ES & Waldor MK (2003) Distinct replication requirements
for the two Vibrio cholerae chromosomes. Cell 114: 521–530.
Egan ES, Lbner-Olesen A & Waldor MK (2004) Synchronous
replication initiation of the two Vibrio cholerae chromosomes.
Curr Biol 14: R501–R502.
FEMS Microbiol Rev 31 (2007) 378–387
385
Replication regulation
Errington J, Murray H & Wu LJ (2005) Diversity and redundancy
in bacterial chromosome segregation mechanisms. Phil Trans
R Soc B 360: 497–505.
Erzberger JP, Pirruccello MM & Berger JM (2002) The structure
of bacterial DnaA: implications for general mechanisms
underlying DNA replication initiation. EMBO J 21:
4763–4773.
Erzberger JP, Mott ML & Berger JM (2006) Structural basis for
ATP-dependent DnaA assembly and replication-origin
remodeling. Nat Struct Mol Biol 13: 676–683.
Felczak MM, Simmons LA & Kaguni JM (2005) An essential
tryptophan of Escherichia coli DnaA protein functions in
oligomerization at the E. coli replication origin. J Biol Chem
280: 24627–24633.
Fol M, Chauhan A, Nair NK, Malone E, Moomey M, Jagannath
C, Madiraju MV & Rajagopalan M (2006) Modulation of
Mycobacterium tuberculosis proliferation by MtrA, an essential
two-component response regulator. Mol Microbiol 60:
643–657.
Foster J, Ganatra M, Kamal I et al. (2005) The Wolbachia genome
of Brugia malayi: endosymbiont evolution within a human
pathogenic nematode. PLoS Biol 3e121: 599–612.
Fukuoka T, Moriya S, Yoshikawa H & Ogasawara N (1990)
Purification and characterization of an initiation protein for
chromosomal replication, DnaA, in Bacillus subtilis. J Biochem
107: 732–739.
Gil R, Silva FJ, Zientz E et al. (2003) The genome sequence of
Blochmannia floridanus: comparative analysis of reduced
genomes. Proc Natl Acad Sci USA 100: 9388–9393.
Gon S, Camara JE, Klungsoyr HK, Crooke E, Skarstad K &
Beckwith J (2006) A novel regulatory mechanism couples
deoxyribonucleotide synthesis and DNA replication in
Escherichia coli. EMBO J 25: 1137–1147.
Goranov AI, Katz L, Breier AM, Burge ChB & Grossman AD
(2005) A transcriptional response to replication status
mediated by the conserved bacterial replication protein DnaA.
Proc Natl Acad Sci USA 102: 12932–12937.
Gorbatyuk B & Marczynski GT (2005) Regulated degradation of
chromosome replication proteins DnaA and CtrA in
Caulobacter crescentus. Mol Microbiol 55: 1233–1245.
Han JS, Park JY, Lee YS, Thony B & Hwang DS (1999) PhoBdependent transcriptional activation of the iciA gene during
starvation for phosphate in Escherichia coli. Mol Gen Genet
262: 448–452.
Hayashi M, Ogura Y, Harry EJ, Ogasawara N & Moriya S (2005)
Bacillus subtilis YabA is involved in determining the timing and
synchrony of replication initiation. FEMS Microbiol Lett 247:
73–79.
Heidelberg JF, Eisen JA, Nelson WC et al. (2000) DNA sequence
of both chromosomes of the cholera pathogen Vibrio cholerae.
Nature 406: 469–470.
Holtzendorff J, Hung D, Brende P, Reisenauer A, Viollier PH,
McAdams HH & Shapiro L (2004) Oscillating global
regulators control the genetic circuit driving a bacterial cell
cycle. Science 304: 983–987.
FEMS Microbiol Rev 31 (2007) 378–387
Holtzendorff J, Reinhardt J & Viollier PH (2006) Cell cycle
control by oscillating regulatory proteins in Caulobacter
crescentus. BioEssays 28: 355–361.
Hoskisson PA & Hutchings MI (2006) MtrAB-LpqB: a conserved
three-component system in actinobacteria? Trends Microbiol
14: 444–449.
Hottes AK, Shapiro L & McAdams HH (2005) DnaA coordinates
replication initiation and cell cycle transcription in
Caulobacter crescentus. Mol Microbiol 58: 1340–1353.
Hung DY & Shapiro L (2002) A signal transduction protein cues
proteolytic events critical to Caulobacter cell cycle progression.
Proc Natl Acad Sci USA 99: 13160–13165.
Hwang DS & Kornberg A (1992) Opening of the replication
origin of Escherichia coli by DnaA protein with protein HU or
IHF. J Biol Chem 267: 23083–23086.
Ishida T, Akimitsu N, Kashioka T, Hatano M, Kubota T, Ogata Y,
Sekimizu K & Katayama T (2004) DiaA, a novel DnaA-binding
protein, ensures the timely initiation of Escherichia coli
chromosome replication. J Biol Chem 279: 45546–45555.
Iuchi S & Weiner L (1996) Cellular and molecular physiology of
Escherichia coli in the adaptation to aerobic environments.
J Biochem 120: 1055–1063.
Jakimowicz D, Chater K & Zakrzewska-Czerwińska J (2002) The
ParB protein of Streptomyces coelicolor A3(2) recognizes a
cluster of parS sequences within the origin-proximal region of
the linear chromosome. Mol Microbiol 45: 1365–1377.
Jakimowicz D, Gust B, Zakrzewska-Czerwińska J & Chater C
(2005) Developmental-stage-specific assembly of ParB
complexes in Streptomyces coelicolor hyphae. J Bacteriol 187:
3572–3580.
Jenal U & Fuchs T (1998) An essential protease involved in
bacterial cell-cycle control. EMBO J 17: 5658–5669.
Jensen RB (2006) Coordination between chromosome
replication, segregation, and cell division in Caulobacter
crescentus. J Bacteriol 188: 2244–2253.
Kaguni JM (2006) DnaA: controlling the initiation of bacterial
DNA replication and more. Annu Rev Microbiol 60: 351–371.
Kahng LS & Shapiro L (2001) The CcrM DNA methyltransferase
of Agrobacterium tumefaciens is essential, and its activity is cell
cycle regulated. J Bacteriol 181: 3065–3075.
Katayama T (2001) Feedback controls restrain the initiation of
Escherichia coli chromosomal replication. Mol Microbiol 41:
9–17.
Katayama T, Kubota T, Kurokawa K, Crooke E & Sekimizu K
(1998) The initiator function of DnaA protein is negatively
regulated by the sliding clamp of the E. coli chromosomal
replicase. Cell 94: 61–71.
Kato J (2005) Regulatory network of the initiation of
chromosomal replication in Escherichia coli. Critical Rev
Biochem Mol Biol 40: 331–342.
Kato J & Katayama T. (2001) Hda, a novel DnaA-related protein,
regulates the replication cycle in Escherichia coli. EMBO J 20:
4253–4262.
Kim MS, Bae SH, Yun SH et al. (2005) Cnu, a novel oriC-binding
protein of Escherichia coli. J Bacteriol 187: 6998–7008.
2007 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
c
386
Kim S, Dallmann HG, McHenry CS & Marians KJ (1996)
Coupling of a replicative polymerase and helicase: a tau–DnaB
interaction mediates rapid replication fork movement. Cell 84:
643–650.
Kitagawa R, Ozaki T, Moriya S & Ogawa T (1998) Negative
control of replication initiation by a novel chromosomal locus
exhibiting exceptional affinity for Escherichia coli DnaA
protein. Genes Dev 12: 3032–3043.
Konieczny I. (2003) Strategies for helicase recruitment and
loading in bacteria. EMBO Rep 4: 37–41.
Lee DG & Bell SP (2000) ATPase switches controlling DNA
replication initiation. Curr Opin Cell Biol 3: 280–285.
Lee PS & Grossman AD (2006) The chromosome partitioning
proteins Soj (ParA) and Spo0J (ParB) contribute to accurate
chromosome partitioning, separation of replicated sister
origins, and regulation of replication initiation in Bacillus
subtilis. Mol Microbiol 60: 853–869.
Lee PS, Lin DCH, Shigeki MS & Grossman AD (2003) Effects of
the chromosome partitioning protein Spo0J (ParB) on oriC
positioning and replication initiation in Bacillus subtilis.
J Bacteriol 185: 1326–1337.
Lee YS, Han JS, Jeon Y & Hwang DS (2001) The Arc twocomponent signal transduction system inhibits in vitro
Escherichia coli chromosomal initiation. J Biol Chem 276:
9917–9923.
Leonard AC & Grimwade JE (2005) Building a bacterial orisome:
emergence of new regulatory features for replication origin
unwinding. Mol Microbiol 55: 978–985.
Lobner-Olesen A, Skovgaard O & Marinus MG (2005) Dam
methylation: coordinating cellular processes. Curr Opin
Microbiol 8: 154–160.
Lu Y-B, Ratnakar PVAL, Mohanty B. & Bastia D (1996) Direct
physical interaction between DnaG primase and DnaB helicase
of Escherichia coli is necessary for optimal synthesis of primer
RNA. Pro. Natl Aca Sci USA 93: 12902–12907.
Maaloe O & Kjeldgaard NO (1966) Control of Macromolecular
Synthesis. W.A. Benjamin, Inc., New York, NY.
Mackiewicz P, Zakrzewska-Czerwiñska J, Zawilak A, Dudek MR
& Cebrat S (2004) Where does bacterial replication start? Rules
for predicting the oriC region. Nucl Acids Res 32: 3781–3791.
Madiraju MVV, Moomey M, Neuenschwander PF,
Muniruzzaman S, Yamamoto K, Grimwade JE & Rajagopalan
M (2006) The intrinsic ATPase activity of Mycobacterium
tuberculosis DnaA promotes its rapid oliogmerization on oriC.
Mol Microbiol 59: 1876–1890.
Majka J, Messer W, Schrempf H & Zakrzewska-Czerwińska J
(1997) Purification and characterization of the Streptomyces
lividans initiator protein DnaA. J Bacteriol 179: 2426–2432.
Marczynski GT & Shapiro L (2002) Control of chromosome
replication in Caulobacter crescentus. Annu Rev Microbiol 56:
625–656.
Margolin W & Bernander R (2004) How do prokaryotic cells
cycle? Curr Biol 14: R768–R770.
2007 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
c
J. Zakrzewska-Czerwińska et al.
McAdams HH & Shapiro L (2003) A bacterial cell-cycle
regulatory network operating in time and space. Science 301:
1874–1877.
McGrath PT, Viollier P & McAdams HH (2004) Setting the pace:
mechanisms tying Caulobacter cell-cycle progression to
macroscopic cellular events. Curr Opin Microbiol 7: 192–197.
Mergaert P, Uchiumi T, Alunni B et al. (2006) Eukaryotic control
on bacterial cell cycle and differentiation in the Rhizobiumlegume symbiosis. Proc Natl Acad Sci USA 103: 5230–5235.
Messer W & Weigel C (1997) DnaA initiator–also a transcription
factor. Mol Microbiol 24: 1–6.
Messer W (2002) The bacterial replication initiator DnaA. DnaA
& oriC, the bacterial mode to initiate DNA replication. FEMS
Microbiol Rev 26: 355–374.
Moran NA (2002) Microbial minimalism: genome reduction in
bacterial pathogens. Cell 108: 583–586.
Moriya S, Ima Y, Hassan AK & Ogasawara N (1999) Regulation of
initiation of Bacillus subtilis chromosome replication. Plasmid
41: 17–29.
Mukhopadhyay S & Chattoraj DK (2000) Replication-induced
transcription of an autorepressed gene: the replication
initiator gene of plasmid P1. Proc Natl Acad Sci USA 97:
7142–7147.
Murray H, Ferreira H & Errington J (2006) The bacterial
chromosome segregation protein Spo0J spreads along DNA
from parS nucleation sites. Mol Microbiol 61: 1352–1361.
Noirot-Gros MF, Dervyn E, Wu LJ, Mervelet P, Errington J,
Ehrlich SD & Noirot P (2002) An expanded view of bacterial
DNA replication. Proc Natl Acad Sci USA 99: 8342–8347.
Noirot-Gros MF, Velten M, Yoshimura M, McGovern S,
Morimoto T, Ehrlich SD, Ogasawara N, Polard P & Noirot P
(2006) Functional dissection of YabA, a negative regulator of
DNA replication initiation in Bacillus subtilis. Proc Natl Acad
Sci USA 103: 2368–2373.
Ogura Y, Imai Y, Ogasawara N & Moriya S (2001) Autoregulation
of the dnaA–dnaN operon and effects of DnaA protein levels
on replication initiation in Bacillus subtilis. J Bacteriol 183:
3833–3841.
Ozaki S, Fujimitsu K, Kurumizaka H & Katayama T (2006) The
DnaA homolog of the hyperthermophilic eubacterium
Thermotoga maritima forms an open complex with a minimal
149-bp origin region in an ATP-dependent manner. Genes
Cells 11: 425–438.
Park K, Han E, Paulsson J & Chattoraj DK (2001) Origin pairing
(‘handcuffing’) as a mode of negative control of P1 plasmid
copy number. EMBO J 20: 7323–7332.
Paulsson J & Chattoraj DK (2006) Origin inactivation in bacterial
DNA replication control. Mol Microbiol 61: 9–15.
Quon KC, Yang B, Domian IJ, Shapiro L & Marczynski GT (1998)
Negative control of bacterial DNA replication by a cell cycle
regulatory protein that binds at the chromosome origin. Proc
Natl Acad Sci USA 95: 120–125.
Riber L, Olsson JA, Jensen RB, Skovgaard O, Dasgupta S, Marinus
MG & Lobner-Olesen A (2006) Hda mediated inactivation of
the DnaA protein and dnaA gene autoregulation act in concert
FEMS Microbiol Rev 31 (2007) 378–387
387
Replication regulation
to ensure homeostatic maintenance of the Escherichia coli
chromosome. Genes Dev 20: 2121–2134.
Robinson NP & Bell SD (2005) Origins of DNA replication in the
three domains of life. FEBS J 272: 3757–3766.
Ruban-Osmialowska B, Jakimowicz D, Smulczyk-Krawczyszyn A,
Chater KF & Zakrzewska-Czerwińska J (2006) Replisome
localization in vegetative and aerial hyphae of Streptomyces
coelicolor. J Bacteriol 188: 7311–7316.
Ryan VT, Grimwade JE, Camara JE, Crooke E & Leonard AC
(2004) Escherichia coli prereplication complex assembly is
regulated by dynamic interplay among Fis, IHF and DnaA.
Mol Microbiol 51: 1347–1359.
Schaeffer PM, Headlam MJ & Dixon NE (2005) Protein–protein
interactions in the eubacterial replisome. IUBMB Life 57: 5–12.
Schaper S, Nardmann J, Lüder G, Lurz R, Speck C & Messer W
(2000) Identification of the chromosomal replication origin
from Thermus thermophilus and its interaction with the
replication initiator DnaA. J Mol Biol 299: 655–665.
Siam R & Marczynski GT (2000) Cell cycle regulator
phosphorylation stimulates two distinct modes of binding at a
chromosome replication origin. EMBO J 19: 1138–1147.
Smulczyk-Krawczyszyn A, Jakimowicz D, Ruban-Ośmiałowska B,
Zawilak-Pawlik A, Majka J, Chater K & ZakrzewskaCzerwińska J (2006) Cluster of DnaA boxes involved in the
regulation of Streptomyces chromosome replication: from in
silico to in vivo studies. J Bacteriol 188: 6184–6194.
Speck C & Messer W (2001) Mechanism of origin unwinding:
sequential binding of DnaA initiator protein to doublestranded and single-stranded DNA in the AT-rich region of the
replication origin. EMBO J 20: 1469–1476.
Speck C, Chen Z, Li H & Stillman B (2005) ATPase-dependent
cooperative binding of ORC and Cdc6 to origin DNA. Nat
Struct Mol Biol 12: 965–971.
Stephens C, Reisenauer A, Wright R & Shapiro L (1996) A cell
cycle-regulated bacterial DNA methyltransferase is essential
for viability. Proc Natl Acad Sci USA 93: 1210–1214.
Stephens CM, Zweiger G & Shapiro L (1995) Coordinate cell
cycle control of a Caulobacter DNA methyltransferase
FEMS Microbiol Rev 31 (2007) 378–387
and the flagellar genetic hierarchy. J Bacteriol 177:
1662–1669.
Tougu K & Marians KJ (1996) The extreme C terminus of
primase is required for interaction with DnaB at the
replication fork. J Biol Chem 271: 21391–21397.
Weigel C, Schmidt A, Ruckert B, Lurz R & Messer W (1997)
DnaA protein binding to individual DnaA boxes in the
Escherichia coli replication origin, oriC. EMBO J 16:
6574–6583.
Weigel C, Schmidt A, Seitz H, Tungler D, Welzeck M & Messer W
(1999) The N-terminus promotes oligomerization of the
Escherichia coli initiator protein DnaA. Mol Microbiol 34:
53–66.
Wortinger M, Sackett MJ & Brun YV (2000) CtrA mediates a
DNA replication checkpoint that prevents cell division in
Caulobacter crescentus. EMBO J 19: 4503–4512.
Wu D, Daugherty SC, Aken SE et al. (2006) Metabolic
complementarity and genomics of the dual bacterial
symbiosis of sharpshooters. PLoS Biol 6e188:
1079–1092.
Yamamoto K, Muniruzzaman S, Rajagopalan M & Madiraju MV
(2002) Modulation of Mycobacterium tuberculosis DnaA
protein-adenine-nucleotide interactions by acidic
phospholipids. Biochem J 363: 305–311.
Zakrzewska-Czerwińska J & Schrempf H (1992) Characterization
of an autonomously replicating region from the Streptomyces
lividans chromosome. J Bacteriol 174: 2688–2693.
Zawilak-Pawlik A, Kois A, Majka J, Jakimowicz D, SmulczykKrawczyszyn A, Messer W & Zakrzewska-Czerwinska J (2005)
Architecture of bacterial replication initiation complexes:
orisomes from four unrelated bacteria. Biochem J 389:
471–481.
Zhang W, Allen S, Roberts CJ & Soultanas P (2006) The Bacillus
subtilis primosomal protein DnaD untwists supercoiled DNA.
J Bacteriol 188: 5487–5493.
Zhang W, Carneiro MJVM, Turner IJ, Allen S, Roberts CJ &
Soultanas P (2005) The Bacillus subtilis DnaD and DnaB
proteins exhibit different DNA remodeling activities.
J Mol Biol 351: 66–75.
2007 Federation of European Microbiological Societies
Published by Blackwell Publishing Ltd. All rights reserved
c