Available online at www.sciencedirect.com
Players between the worlds: multifunctional DNA translocases
Christine Kaimer2 and Peter L Graumann1,3
DNA translocases play important roles during the bacterial cell
cycle and in cell differentiation. Escherichia coli cells contain a
multifunctional translocase, FtsK, which is involved in cell
division, late steps of chromosome segregation and dimer
resolution. In Gram-positive bacteria, the latter two processes
are achieved by two translocases, SftA and SpoIIIE. These two
translocases operate in a two step fashion, before and after
closure of the division septum. DNA translocases have the
remarkable ability to translocate DNA in a vectorial manner,
orienting themselves according to polar sequences present in
bacterial genomes, and perform various additional roles during
the cell cycle. DNA translocases genetically interact with
Structural Maintenance of Chromosomes (SMC) proteins in a
flexible manner in different species, underlining the high
versatility of this class of proteins.
Addresses
1
Mikrobiologie, Fakultät für Biologie, Universität Freiburg,
Schänzlestraße 1, 79104 Freiburg, Germany
2
Department of Molecular and Cellular Biology, University of California,
Berkeley, CA 94720, USA
3
SYNMIKRO, University of Marburg, Germany
Corresponding author: Graumann, Peter L
([email protected])
Current Opinion in Microbiology 2011, 14:719–725
This review comes from a themed issue on
Growth and Development: Prokaryotes
Edited by Martin Thanbichler
Available online 31st October 2011
1369-5274/$ – see front matter
# 2011 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.mib.2011.10.004
Structure and function of DNA translocases
(usually termed ‘dif’ site) that is recognized by two DNA
recombinases to yield efficient recombinational resolution of the dimer and ii) relies on the fact that the
terminus of the chromosome is the last region to be
separated and is positioned in the cell centre. DNA
translocases that are recruited to the division septum at
the mid-cell area specifically move DNA surrounding the
terminus region towards the septum, such that the dif
sites are juxtaposed for efficient recombination [3].
Thirdly, during sporulation, the Bacillus subtilis cell
divides asymmetrically by laying down a septum close
to one cell pole, which closes over one of the two
replicated chromosomes. A defined one third portion of
the chromosome is inside the small cell compartment
(forespore), while the remaining two thirds (2.8 Mbp of
DNA) must be actively moved into the spore by the
SpoIIIE DNA translocase [4–6].
All known DNA translocases are AAA-type ATPases that
share a conserved C-terminal domain of about 500 residues (Figure 1). This domain achieves efficient and
highly processive DNA translocation, which is powered
through ATP binding and DNA-dependent hydrolysis by
the a and b subdomains [7]. DNA translocases generally
assemble into a ring-shaped hexamer, accommodating the
DNA double strand in a central channel [8]. A conserved
region at the C-terminus of the translocase (the g subdomain) recognizes specific DNA sequences that determine the direction of DNA translocation [9,10]
(Figure 1). It was shown that SpoIIIE and FtsK strip
off proteins from the DNA as they translocate, verifying
that the tight channel formed by the C-terminal domain is
only permissive for DNA [11,12]. In the case of
SpoIIIE, this effect might be significant for developmental gene expression in the forespore [11].
DNA translocation is most relevant towards the end of the
bacterial cell cycle, or during development. Although
chromosome segregation occurs rather efficiently in exponentially growing cells, some DNA can lag behind and
remain in the vicinity of the closing division septum,
likely to be damaged. The rescue of such septum-trapped
chromosomes requires the action of DNA translocases,
which complete segregation into the daughter cells [1,2].
Most DNA translocases contain several membrane-spanning regions at their N-terminus (Figure 1), and some were
shown to form a pore for DNA transport across membranes
[13,14]. The N-terminal part of DNA translocases often
mediates a function unrelated to DNA translocation. For
example, the FtsK N-terminus recruits several cell division
proteins [15,16], while in SpoIIIE it is required for membrane fusion/fission during sporulation [17]. Thus, many
DNA translocases are multifunctional proteins.
Secondly, uneven events of recombination between circular sister chromosomes result in the formation of a
single dimeric chromosome that cannot be separated.
The trick to resolve such a chromosome dimer lies in a
system that i) employs a specific site close to the terminus
The N-terminal and C-terminal domains are connected
by a linker that is highly variable in length (Figure 1).
E. coli FtsK, for instance, has a very long linker with
repetitive sequence motifs. While the function of the
FtsK linker has long been elusive, Dubarry et al. recently
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Current Opinion in Microbiology 2011, 14:719–725
720 Growth and Development: Prokaryotes
Figure 1
DNA translocase
FtsK
E. coli
1329
1
TraB (pSVH1)
S. coelicolor
β
γ
α
β
γ
α
β
γ
α
β
γ
787
1
SpoIIIE
B. subtilis
SftA
B. subtilis
α
1
952
1
774
ATP-binding
DNA recognition
Current Opinion in Microbiology
Examples of the modular arrangement of DNA translocases. Consensus sequences are given for ATP-binding and DNA-binding motifs. Black bars
indicate transmembrane helices.
provided insight in its role in coordinating cell division.
The authors elegantly used a suppressor mutant background to study the effects of fusions of several FtsKlinker segments to other cell division proteins [18].
Apparently, different regions of the FtsK-linker interact
specifically with several divisome components. Their
observations led to intriguing considerations about the
role of FtsK as a cell division checkpoint, which might
delay division when segregation has not been finished,
thereby coupling cell division and chromosome segregation [18,19].
Directed DNA translocation is determined by
short polar sequences – a common theme
In order to carry out their specific functions in the cell
cycle, DNA translocases must transport the chromosome
reliably in a certain direction, for example, away from the
closing septum, from the mother cell into the forespore or
to align the dif sites at chromosome termini [20]
(Figure 2A). Directional transport is determined by short,
asymmetric sequences on the chromosome that are polarized towards the terminus region [21–23] (Figure 2B).
Single molecule experiments, as well as bioinformatic
analysis identified the orienting sequences for DNA
translocation by E. coli FtsK (KOPS) and B. subtilis
SpoIIIE (SRS) [24,25]. Mutants that are no longer able
to recognize KOPS sequences are compromised in the
late stages of chromosome processing, confirming the
significance of short polar sequences for FtsK function
in vivo [26]. Similarly, SRS sequences were shown to be
required for directed DNA translocation by SpoIIIE and
Current Opinion in Microbiology 2011, 14:719–725
for efficient sporulation [25] (Figure 2A). Short polar
sequences are conserved in many other bacterial species,
suggesting a common translocation mechanism.
Recent progress has been made to further elucidate the
molecular mechanism used by DNA translocases, in
particular addressing the role of ATP binding and
hydrolysis for DNA translocation. Initially, single molecule experiments had suggested that FtsK would reverse
Figure 2
(a)
(b)
oriC
cell division
chromosome dimer
resolution
circular
chromosome
ter dif
sporulation
KOPS (E. coli)
SRS (B. subtilis)
conjugation
Current Opinion in Microbiology
(A) Different functions of DNA translocases. (B) Illustration of the
arrangement of polar sequences mediating sequence-directed
assembly/translocation. Note that many more polar sequences than
indicated exist on the E. coli and B. subtilis chromosomes and at low
frequency, sequences are oriented away from the ‘ter’-site (terminus
region on the chromosome).
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Multifunctional DNA translocases Kaimer and Graumann 721
the direction of DNA translocation when a KOPS
sequence in non-permissive orientation is encountered
[23,25]. However, structural analysis of the FtsKg domain
bound to DNA indicated that FtsKg recognizes KOPS in
one orientation only [9]. It was hypothesized that KOPS
sequences serve as efficient loading sites that orient FtsK
on the chromosome, instead of actively causing a switch in
translocation direction. In a recent report, Graham et al.
provide evidence that FtsK assembles specifically at KOPS
sequences and does not recognize non-permissive KOPS
during translocation, confirming that KOPS are merely
loading sites for FtsK [27]. The authors used stoppedflow techniques to separate the dsDNA translocation and
ATPase activities of FtsK on a millisecond timescale. They
further presented a kinetic model for FtsK assembly predicting a coupling efficiency of 2 bp DNA transported
per hydrolyzed ATP.
In another report, Crozat et al. provided valuable insight
in the interplay between subunits in a FtsK hexamer
[12]. The authors constructed covalently linked dimers
and trimers of the FtsK catalytic subunits, which
assembled into functional hexamers. Then, they systematically introduced catalytic point mutations into specific
subunits and tested for DNA translocation activity. Surprisingly, mixed hexamers of active and inactive FtsK
subunits are not compromised in DNA translocation, but
unable to displace protein roadblocks from the DNA. The
authors conclude that FtsK does not follow a stochastic or
a concerted mechanism like other ring shaped molecular
motors. They propose a sequential mechanism for DNA
translocation where different nucleotide-binding states
cause an asymmetry that is propagated around the ring as
DNA is translocated. Since the translocase unit is highly
conserved among DNA translocases, these findings on E.
coli FtsK are probably applicable for most members of the
FtsK/SpoIIIE translocase family.
SpoIIIE and TraB transport DNA across two
membranes
Important insight into the mode of DNA translocation
was also achieved by in vivo experiments on B. subtilis
SpoIIIE. The Rudner laboratory showed that during
sporulation, SpoIIIE moves DNA across two adjacent
membranes (Figure 3B), rather than through a gap at
the incompletely closed septal membrane [13]. These
findings suggest that transport is driven by two hexamers,
one within each membrane, which must communicate
with each other, and only one must actively pump DNA
while the other may simply constitute a membrane pore
(although it is possible that it may have to hydrolyze ATP
to undergo the conformational changes required for translocation). Visualization of two chromosomal sites showed
that both arms of the chromosome are simultaneously
moved into the forespore, supporting the view that two
translocation channels operate in a coordinated manner.
Recently, Fleming et al. employed live-cell PALM
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Figure 3
(a)
FtsZ
SftA
SpolllE
(b)
Current Opinion in Microbiology
(A) Function of DNA translocases during the cell cycle. (B) Model for
double hexamers of SpoIIIE translocating DNA into the forspore during
sporulation in B. subtilis. Arrows indicate the direction of DNA transport.
(photo activation light microscopy) and other microscopy
techniques to further characterize the assembly of the
SpoIIIE translocation pore at the sporulation septum
[17]. Their data suggest several steps in SpoIIIE assembly: first, the transmembrane domain mediates localization to the leading edge of the closing septum, where an
unstable channel is formed. The channel is stabilized
when DNA is bound by the translocase domains, and the
chromosome is translocated through the separated membranes. Towards the end of chromosome translocation,
release of the DNA by the translocase domain destabilizes the channel, which provides a larger opening that
allows the final loop of the circular chromosome to pass
into the forespore. After the entire chromosome is within
the forespore, the mother cell membrane starts move
around the forespore membrane, finally completely
engulfing the smaller cell. SpoIIIE travels with the leading edge of the mother cell membrane and is essential for
membrane fusion [17,28]. Thus, SpoIIIE is a truly
bifunctional protein.
In contrast to SpoIIIE, the transmembrane domain of
FtsK is dispensable for its function in vivo [29]. FtsK can
efficiently support chromosome segregation and dimer
Current Opinion in Microbiology 2011, 14:719–725
722 Growth and Development: Prokaryotes
resolution when it is located to the division septum by an
adaptor protein, suggesting that FtsK does not form a
membrane channel during cell division. Furthermore, a
second B. subtilis DNA translocase, SftA, and its homologues lack any membrane spanning domains (see below).
On the contrary, membrane pore formation was experimentally confirmed for Streptomyces coelicolor TraB [14].
Apparently, different modes exist for DNA translocation
across membranes or within a cell, which need to be
further characterized.
During conjugation, DNA is moved across two (or more in
Gram-negative bacteria) membranes from donor to recipient (Figure 2A). S. coelicolor TraB is encoded on a
conjugational plasmid and is a genuine DNA translocase
that drives the sequence-specific translocation of double
stranded DNA from one cell to another in a conjugationlike mechanism. So far, conjugation had been known to
involve the transport of ssDNA from donor to recipient
cell, where it is converted back to dsDNA. Translocation
is mediated through a type IV secretion-like system that
also involves DNA translocase-like proteins. However,
Streptomycetes transport dsDNA, and therefore have a
distinct conjugation machinery. TraBs are encoded on
different conjugative plasmids and are diverse in
sequence, showing only 20% identity with FtsK/
SpoIIIE, mainly in the translocase domain. Similarly to
other translocases, the C-terminal domain of TraB recognizes 8-bp oriented sequences (TRS) found close to the
clt region on the conjugational plasmid, and requires these
so-called clc sequences for DNA binding [14]. The
protein is a hexamer and forms pores in lipid bilayers.
However, the mechanism of its assembly at the hyphal tip
must be different from that of FtsK/SpoIIIE proteins,
because the tip lacks a division machinery or membraneentrapped DNA.
A two step translocase system in Grampositive bacteria
It has recently become clear that B. subtilis employs two
distinct DNA translocases to couple late stages of
chromosome segregation with cell division [30,31].
Besides SpoIIIE, B. subtilis contains an orf encoding
for a protein, whose C-terminus is very similar to that
of SpoIIIE, but without any membrane-spanning sections
in the N-terminal region. Indeed, the protein, termed
SftA, is soluble, but it is targeted to the FtsZ ring very
early during cell division (Figure 3A). An elegant experimental setup showed that SftA moves DNA before
closure of the septum, while SpoIIIE only accumulates
at the closed septum when DNA is entrapped and moves
DNA through the two adjacent membranes, analogous to
sporulation [30] (Figure 3A). SftA should be able to move
DNA in a sequence directed manner during cytokinesis,
but its recognition sequence has not yet been identified.
Both systems act synergistically, and loss of both translocases exacerbates all phenotypes, that is, segregation
Current Opinion in Microbiology 2011, 14:719–725
defects and sensitivity to DNA damaging agents. Many
Gram-positive bacteria possess two DNA translocases,
suggesting that instead of a single FtsK-like protein,
many bacteria have opted to use two independent
DNA translocases to secure chromosome segregation
and also achieve efficient chromosome dimer resolution.
A further, cell cycle-related function of DNA translocases
is the restart of the cell cycle upon a transient arrest in cell
division induced by DNA damage. B. subtilis cells lacking
either SpoIIIE or SftA are more sensitive to DNA-damaging agents [31,32], which induce an SOS response and
chromosome decondensation. Cell viability drops markedly if DNA is not moved away from the septum upon
resumption of growth.
Dimer resolution
During late stages of the cell cycle, DNA translocases
assist in the resolution of covalently linked chromosomes
(dimers). Although more information emerges on dimer
resolution in different species [33], the most detailed
view on a molecular level is available for E. coli, where the
process was first identified and characterized [3,34]. Dimer resolution in E. coli requires two site-specific recombinases, XerC and XerD, bound to the dif site, and the
DNA translocase FtsK. In addition to aligning the dif sites
by KOPS-guided DNA translocation, FtsK also directly
activates XerD by protein–protein interaction [35,36].
The g subdomain of FtsK stimulates XerD to form a
Holliday junction that is subsequently resolved by XerC
[37]. Interaction between FtsK and XerD is promoted by
specific DNA binding sites surrounding the dif site [38].
Interestingly, it was observed that FtsK not only translocates fast towards the dif sites, but also specifically stops
when the site-specific recombinases are reached [39].
This avoids that FtsK, a powerful molecular motor, strips
the recombinases from the DNA, which would prevent
dimer resolution. It is not yet clear how translocation is
specifically stopped, but the process involves reducing
the ATPase activity of FtsK.
The general process of chromosome dimer resolution by
site-specific recombination seems to be widely conserved.
Both DNA translocases and site-specific recombinases are
found in many species [40]. Furthermore, a recent publication presents a phylogenetic approach to predict the
chromosomal dif site, which was identified in 641 organisms within 16 different phyla [41]. However, there are
also considerable variations among the dimer resolution
systems. B. subtilis apparently employs both of his DNA
translocases, SpoIIIE and SftA, for alignment of the dif
site, but none of them seems to be required for activation
of the site-specific recombinases, RipX and CodV [42]. In
this system, RipX and CodV are present at the dif site
throughout the cell cycle, such that dimer resolution can
instantly occur upon juxta-positioning of dif sites. In
Streptococcus and Lactococcus strains, dimer resolution is
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Multifunctional DNA translocases Kaimer and Graumann 723
mediated by a single site-specific recombinase, XerS,
which needs to be activated by a FtsK homologue
[43,44]. Studies on chromosome dimer resolution were
also extended to archaeal species: both Pyrococcus abyssi
and Sulfolobus solfataricus use a single site-specific recombinase for dimer resolution, but lack a FtsK-like DNA
translocase [45,46]. Surprisingly, short polar sequences
(ASPS, archaeal short polar sequences) oriented towards
the dif site were identified in Pyrococcus. It will be interesting to learn more about the function of DNA translocation in archaeal dimer resolution and to perhaps
identify a novel class of translocases unrelated to FtsK.
Interplay between the SMC/MukB complex
and DNA translocases
SMC proteins play a key role in chromosome segregation
in eukaryotic cells and in many bacteria. In the absence of
SMC (or its analogue MukB in E. coli) or of the other two
components of the SMC complex, ScpA and ScpB (MukF
and MukE), cells can only grow extremely slowly and do
not properly separate duplicated chromosome regions.
The link to DNA translocases comes from the fact that
smc spoIIIE or smc sftA double deletions or a mukB/truncated ftsK combination are lethal, revealing that the smc
(mukB) null cells can only grow because non-segregated
chromosomes are tediously moved by DNA translocases,
which is inefficient at faster growth rates (e.g. above 23 8C
in rich medium). Recently, it has become clear that
several bacterial species can live rather well without
SMC, like Mycobacterium tuberculosis or Staphylococcus aureus [47,48]. In the latter, an additional spoIIIE deletion
does not further increase the high number of anucleate
cells observed in smc single mutant cells. However, it
renders the cells temperature-sensitive for growth, while
smc null cells have no detectable growth defect [48]. It
remains an intriguing question if another DNA translocase may rescue the defects generated through the
spoIIIE deletion in the Dsmc background, and if DNA
translocases may play a more important role in chromosome segregation in this coccus (or even in cocci) than
SMC protein. Two groups have recently investigated the
function of SMC and DNA translocases in S. coelicolor, the
model organism for the group of Streptomycetes that
grow as branched hyphae and form aerial mycelium,
whose tips differentiate into exospores. In contrast to
growth mycelium, which shows extremely relaxed
chromosome segregation and division, in aerial tips, many
chromosomes are duplicated and separated in parallel,
which is rapidly followed by cell division. Here, an ftsK
deletion leads to a considerable segregation defect (15%
anucleate spores), and FtsK localizes to the division septa,
while an smc deletion results in the generation of about
8% anucleate spores, with SMC localizing to the condensing nucleoids [49,50]. No additive effect was seen in the
double mutant strain, indicating redundant functions of
SMC and FtsK. When the smc deletion is combined with
a deletion in another segregation system (ParAB), the
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segregation phenotype is exacerbated (like in B. subtilis),
showing that these two systems are not epistatic, but
when ftsK is deleted on top of smc and parB, the segregation defect is reduced relative to the double mutant
combinations [49]. These experiments reveal an intricate
interplay between different segregation proteins in Streptomycetes and show that there must be another chromosome segregation system out there, which has not yet
been described. Interestingly, another DNA translocase,
SffA, accumulates specifically at sporulation septa, dependent on the membrane protein SmeA, and colocalizes
with FtsK [51]. The loss of SffA resulted in segregation
and septation defects, but SffA did not show redundancy
with FtsK. Thus, SffA appears to function as a distinct
DNA translocase during closure of sporulation septa,
revealing that several bacterial species employ multiple
non-redundant DNA translocases.
Summary
DNA translocases are a class of proteins whose intriguing mechanism is relatively well understood, down to
a molecular level. Their mechanism serves as a model
for other motor proteins and possibly also conjugative
DNA pumps. However, many open questions linger on:
how do translocases bind to DNA? They can be isolated
as hexamers even in the absence of DNA, and such
structures must open up at one position or disintegrate
to bind around the DNA double helix or reassemble on
its substrate. The exact mechanism of power generation
and DNA translocation remain to be elucidated. It is
also still an unresolved question how translocases
involved in the Type IV secretion-like conjugation
apparatus work during transport of ssDNA. Clearly,
DNA tranlocases have many facettes and connect vectorial DNA transfer with many different aspects in the
bacterial cell cycle.
References and recommended reading
Papers of particular interest, published within the period of review,
have been highlighted as:
of special interest
of outstanding interest
1.
Sherratt DJ, Arciszewska LK, Crozat E, Graham JE, Grainge I: The
Escherichia coli DNA translocase FtsK. Biochem Soc Trans
2010, 38:395-398.
2.
Wu LJ: It takes two DNA translocases to untangle
chromosomes from the division septum. Mol Microbiol 2009,
74:773-776.
3.
Sherratt DJ, Soballe B, Barre FX, Filipe S, Lau I, Massey T, Yates J:
Recombination and chromosome segregation. Philos Trans R
Soc Lond B Biol Sci 2004, 359:61-69.
4.
Bath J, Wu LJ, Errington J, Wang JC: Role of Bacillus subtilis
SpoIIIE in DNA transport across the mother cell-prespore
division septum. Science 2000, 290:995-997.
5.
Ben-Yehuda S, Rudner DZ, Losick R: Assembly of the SpoIIIE
DNA translocase depends on chromosome trapping in
Bacillus subtilis. Curr Biol 2003, 13:2196-2200.
6.
Sharp MD, Pogliano K: Role of cell-specific SpoIIIE assembly in
polarity of DNA transfer. Science 2002, 295:137-139.
Current Opinion in Microbiology 2011, 14:719–725
724 Growth and Development: Prokaryotes
7.
Barre FX: FtsK and SpoIIIE: the tale of the conserved tails. Mol
Microbiol 2007, 66:1051-1055.
8.
Massey TH, Mercogliano CP, Yates J, Sherratt DJ, Lowe J:
Double-stranded DNA translocation: structure and
mechanism of hexameric FtsK. Mol Cell 2006, 23:457-469.
Lowe J, Ellonen A, Allen MD, Atkinson C, Sherratt DJ, Grainge I:
Molecular mechanism of sequence-directed DNA loading and
translocation by FtsK. Mol Cell 2008, 31:498-509.
The structure of the gamma domain and functional studies provide
important insight into the sequence-directed movement of translocases.
9.
10. Sivanathan V, Allen MD, de Bekker C, Baker R, Arciszewska LK,
Freund SM, Bycroft M, Lowe J, Sherratt DJ: The FtsK gamma
domain directs oriented DNA translocation by interacting with
KOPS. Nat Struct Mol Biol 2006, 13:965-972.
11. Marquis KA, Burton BM, Nollmann M, Ptacin JL, Bustamante C,
Ben-Yehuda S, Rudner DZ: SpoIIIE strips proteins off the
DNA during chromosome translocation. Genes Dev 2008,
22:1786-1795.
Many elegant experiments show that SpoIIIE moves DNA, but not
proteins, through membranes.
12. Crozat E, Meglio A, Allemand JF, Chivers CE, Howarth M, Venien Bryan C, Grainge I, Sherratt DJ: Separating speed and ability to
displace roadblocks during DNA translocation by FtsK. EMBO
J 2010, 29:1423-1433.
This report provides novel insight into the FtsK translocation mechanism
by a systematic analysis of covalently linked catalytic subunits.
13. Burton BM, Marquis KA, Sullivan NL, Rapoport TA, Rudner DZ:
The ATPase SpoIIIE transports DNA across fused septal
membranes during sporulation in Bacillus subtilis. Cell 2007,
131:1301-1312.
14. Vogelmann J, Ammelburg M, Finger C, Guezguez J, Linke D,
Flotenmeyer M, Stierhof YD, Wohlleben W, Muth G: Conjugal
plasmid transfer in Streptomyces resembles bacterial
chromosome segregation by FtsK/SpoIIIE. EMBO J 2011,
30:2246-2254.
Proof that Streptomyces use a genuine DNA translocase for the process
of DNA transfer between bacteria.
15. Draper GC, McLennan N, Begg K, Masters M, Donachie WD: Only
the N-terminal domain of FtsK functions in cell division. J
Bacteriol 1998, 180:4621-4627.
16. Liu G, Draper GC, Donachie WD: FtsK is a bifunctional protein
involved in cell division and chromosome localization in
Escherichia coli. Mol Microbiol 1998, 29:893-903.
17. Fleming TC, Shin JY, Lee SH, Becker E, Huang KC, Bustamante C,
Pogliano K: Dynamic SpoIIIE assembly mediates septal
membrane fission during Bacillus subtilis sporulation. Genes
Dev 2010, 24:1160-1172.
The authors were able to resolve several steps in the dynamic assembly of
SpoIIIE at the sporulation septum by using different microscopy techniques.
18. Dubarry N, Possoz C, Barre FX: Multiple regions along the
Escherichia coli FtsK protein are implicated in cell division.
Mol Microbiol 2010, 78:1088-1100.
A genetic study that addresses the function of the FtsK linker region and
implies a role for a DNA translocase as a cell division checkpoint.
19. Grainge I: FtsK – a bacterial cell division checkpoint? Mol
Microbiol 2010, 78:1055-1057.
20. Bigot S, Sivanathan V, Possoz C, Barre FX, Cornet F: FtsK, a
literate chromosome segregation machine. Mol Microbiol 2007,
64:1434-1441.
24. Bigot S, Saleh OA, Cornet F, Allemand JF, Barre FX:
Oriented loading of FtsK on KOPS. Nat Struct Mol Biol 2006,
13:1026-1028.
25. Ptacin JL, Nollmann M, Becker EC, Cozzarelli NR, Pogliano K,
Bustamante C: Sequence-directed DNA export guides
chromosome translocation during sporulation in Bacillus
subtilis. Nat Struct Mol Biol 2008, 15:485-493.
Shows that DNA transocation during development in Bacillus subtilis is
also guided by polar sequences on the chromosome.
26. Sivanathan V, Emerson JE, Pages C, Cornet F, Sherratt DJ,
Arciszewska LK: KOPS-guided DNA translocation by FtsK
safeguards Escherichia coli chromosome segregation. Mol
Microbiol 2009, 71:1031-1042.
27. Graham JE, Sherratt DJ, Szczelkun MD: Sequence-specific
assembly of FtsK hexamers establishes directional
translocation on DNA. Proc Natl Acad Sci USA 2010,
107:20263-20268.
This report verifies earlier assumptions on the orientation-specific assembly of FtsK at KOPS and provides a kinetic model that predicts the
coupling efficiency between DNA translocation and ATP hydrolysis.
28. Liu NJ, Dutton RJ, Pogliano K: Evidence that the SpoIIIE
DNA translocase participates in membrane fusion during
cytokinesis and engulfment. Mol Microbiol 2006,
59:1097-1113.
29. Dubarry N, Barre FX: Fully efficient chromosome dimer
resolution in Escherichia coli cells lacking the
integral membrane domain of FtsK. EMBO J 2010, 29:
597-605.
This study provides evidence that the membrane domain is not required
for FtsK function, which is in contrast to the SpoIIIE homologue.
30. Biller SJ, Burkholder WF: The Bacillus subtilis SftA (YtpS) and
SpoIIIE DNA translocases play distinct roles in growing cells
to ensure faithful chromosome partitioning. Mol Microbiol
2009, 74:790-809.
31. Kaimer C, Gonzalez-Pastor JE, Graumann PL: SpoIIIE and a
novel type of DNA translocase, SftA, couple chromosome
segregation with cell division in Bacillus subtilis. Mol Microbiol
2009, 74:810-825.
32. Sharpe ME, Errington J: Postseptational chromosome
partitioning in bacteria. Proc Natl Acad Sci USA 1995,
92:8630-8634.
33. Val ME, Kennedy SP, El Karoui M, Bonne L, Chevalier F, Barre FX:
FtsK-dependent dimer resolution on multiple chromosomes in
the pathogen Vibrio cholerae. PLoS Genet 2008, 4:e1000201.
This work extends analysis of dimer resolution to a bacterium having two
independent chromosomes.
34. Capiaux H, Lesterlin C, Perals K, Louarn JM, Cornet F: A dual role
for the FtsK protein in Escherichia coli chromosome
segregation. EMBO Rep 2002, 3:532-536.
35. Yates J, Zhekov I, Baker R, Eklund B, Sherratt DJ, Arciszewska LK:
Dissection of a functional interaction between the DNA
translocase, FtsK, and the XerD recombinase. Mol Microbiol
2006, 59:1754-1766.
36. Aussel L, Barre FX, Aroyo M, Stasiak A, Stasiak AZ, Sherratt D:
FtsK Is a DNA motor protein that activates chromosome dimer
resolution by switching the catalytic state of the XerC and
XerD recombinases. Cell 2002, 108:195-205.
37. Grainge I, Lesterlin C, Sherratt DJ: Activation of XerCD-dif
recombination by the FtsK DNA translocase. Nucleic Acids Res
2011, 39:5140-5148.
21. Bigot S, Saleh OA, Lesterlin C, Pages C, El Karoui M, Dennis C,
Grigoriev M, Allemand JF, Barre FX, Cornet F: KOPS: DNA motifs
that control E. coli chromosome segregation by orienting the
FtsK translocase. EMBO J 2005, 24:3770-3780.
38. Bonne L, Bigot S, Chevalier F, Allemand JF, Barre FX: Asymmetric
DNA requirements in Xer recombination activation by FtsK.
Nucleic Acids Res 2009, 37:2371-2380.
22. Saleh OA, Perals C, Barre FX, Allemand JF: Fast, DNA-sequence
independent translocation by FtsK in a single-molecule
experiment. EMBO J 2004, 23:2430-2439.
39. Graham JE, Sivanathan V, Sherratt DJ, Arciszewska LK: FtsK
translocation on DNA stops at XerCD-dif. Nucleic Acids Res
2009, 38:72-81.
23. Pease PJ, Levy O, Cost GJ, Gore J, Ptacin JL, Sherratt D,
Bustamante C, Cozzarelli NR: Sequence-directed DNA
translocation by purified FtsK. Science 2005, 307:586-590.
40. Recchia GD, Sherratt DJ: Conservation of xer site-specific
recombination genes in bacteria. Mol Microbiol 1999,
34:1146-1148.
Current Opinion in Microbiology 2011, 14:719–725
www.sciencedirect.com
Multifunctional DNA translocases Kaimer and Graumann 725
41. Kono N, Arakawa K, Tomita M: Comprehensive prediction of
chromosome dimer resolution sites in bacterial genomes.
BMC Genomics 2011, 12:19.
References [45] and [46] offer first insight into the dimer resolution
processes of archeal species.
42. Kaimer C, Schenk K, Graumann PL: Two DNA translocases
synergistically affect chromosome dimer resolution in
Bacillus subtilis. J Bacteriol 2010, 193:1334-1340.
47. Guthlein C, Wanner RM, Sander P, Bottger EC, Springer B: A
mycobacterial smc null mutant is proficient in DNA
repair and long-term survival. J Bacteriol 2008,
190:452-456.
43. Nolivos S, Pages C, Rousseau P, Le Bourgeois P, Cornet F: Are
two better than one? Analysis of an FtsK/Xer recombination
system that uses a single recombinase. Nucleic Acids Res
2010, 38:6477-6489.
48. Yu W, Herbert S, Graumann PL, Gotz F: Contribution of SMC
(structural maintenance of chromosomes) and SpoIIIE to
chromosome segregation in Staphylococci. J Bacteriol 2010,
192:4067-4073.
44. Le Bourgeois P, Bugarel M, Campo N, Daveran-Mingot ML,
Labonte J, Lanfranchi D, Lautier T, Pages C, Ritzenthaler P: The
unconventional Xer recombination machinery of
Streptococci/Lactococci. PLoS Genet 2007, 3:e117.
References [43] and [44] provide insight into single-recombinase systems in Gram-positive bacteria.
49. Dedrick RM, Wildschutte H, McCormick JR: Genetic interactions
of smc, ftsK, and parB genes in Streptomyces coelicolor and
their developmental genome segregation phenotypes. J
Bacteriol 2009, 191:320-332.
45. Cortez D, Quevillon-Cheruel S, Gribaldo S, Desnoues N,
Sezonov G, Forterre P, Serre MC: Evidence for a Xer/dif system
for chromosome resolution in archaea. PLoS Genet 2010,
6:e1001166.
46. Duggin IG, Dubarry N, Bell SD: Replication termination and
chromosome dimer resolution in the archaeon Sulfolobus
solfataricus. EMBO J 2011, 30:145-153.
www.sciencedirect.com
50. Kois A, Swiatek M, Jakimowicz D, Zakrzewska-Czerwinska J:
SMC protein-dependent chromosome condensation during
aerial hyphal development in Streptomyces. J Bacteriol 2009,
191:310-319.
51. Ausmees N, Wahlstedt H, Bagchi S, Elliot MA, Buttner MJ,
Flardh K: SmeA, a small membrane protein with multiple
functions in Streptomyces sporulation including targeting of a
SpoIIIE/FtsK-like protein to cell division septa. Mol Microbiol
2007, 65:1458-1473.
Current Opinion in Microbiology 2011, 14:719–725