There are a large number of proteins involved in the control of eukaryotic DNA replication, which act together to ensure DNA is replicated only once every cell cycle. Key proteins involved in the initiation and elongation phases of DNA replication include the MCM (minchromosome maintenance) proteins, MCM2–MCM7, a family of six related proteins believed to act as the replicative helicase. Genome sequencing has revealed that the archaea possess a simplified set of eukaryotic replication homologues. The complexity of the DNA replication machinery in eukaryotes has led to a number of archaeal species being adapted as model organisms for the study of the DNA replication process. Most archaea sequenced to date possess a single MCM homologue that forms a hexameric complex. Recombinant MCMs from several archaea have been used in the biochemical characterization of the protein, revealing that the MCM complex has ATPase, DNA-binding and -unwinding activities. Unusually, the genome of the methanogenic archaeon Methanococcus maripaludis contains four MCM homologues, all of which contain the conserved motifs required for function. The availability of a wide range of genetic tools for the manipulation of M. maripaludis and the relative ease of growth of this organism in the laboratory makes it a good potential model for studying the role of multiple MCMs in DNA replication.

MCM (minichromosome maintenance) proteins in eukaryotic DNA replication

The initiation of DNA replication from specific sites (origins of replication) must be carefully controlled in order to ensure that DNA is replicated only once during each cell cycle [1]. In eukaryotes, a large number of proteins control the events of DNA replication initiation and elongation. These proteins include the ORC (origin recognition complex), which comprises six separate subunits [2], and Cdc6 (cell division cycle 6), which recruits the MCM protein complex to the origin during the G1-phase of the cell cycle [3]. MCM proteins were first discovered in yeast mutants that were unable to maintain small chromosome-like structures that contained a single origin [4]. Subsequently, six eukaryotic MCMs have been identified: MCM2–MCM7 [5].

Although they were first identified as replication factors, MCMs have subsequently been shown to play a role in other important processes in eukaryotic cells. For example, MCM5 interacts directly with the transcription factor STAT1 (signal transducer and activator of transcription 1), and is essential for STAT1-mediated transcriptional activation [6]. MCMs have also been shown to play a role in cell cycle checkpoint control, functioning as S-phase checkpoint targets. MCM2, MCM3 and MCM7 have been shown to interact directly with proteins in DNA repair pathways [7]. The importance of MCMs in the control of cell proliferation is emphasized by the fact that they are highly overexpressed in many cancers [8]. It has been suggested that the MCM subunits, including MCM2, MCM3, MCM5 and MCM7, represent good biomarkers for use in cancer diagnosis [8]. Since MCM2–MCM7 are down-regulated in quiescent, senescent and differentiated cells, they can be used as markers to identify cells with the potential to proliferate, as well as those actively proliferating. This means that MCM2–MCM7 are useful in identifying pre-cancerous cells before they become malignant, allowing early diagnosis and treatment [9]. The overexpression of MCMs in a wide range of cancers means that, as well as being useful diagnostic and prognostic biomarkers, the MCM subunits represent possible targets for anticancer drugs (for a review, see [10]). However, a detailed understanding of MCM2–MCM7 structure and its function at the molecular level, as well as its precise role in DNA replication, is required before the rational design of MCM-inhibitory drugs is possible.

MCMs play an essential role in both the initiation of replication and progression of the replication fork [11]. It has been suggested that MCM2–MCM7 provides the helicase activity required to unwind DNA during replication and is responsible for the initial melting of DNA at replication origins (for a review, see [12]). However, the individual roles of each of the six subunits, and the mechanism(s) by which they use energy obtained by ATP hydrolysis to separate the DNA duplex are unknown. Experiments using yeast degron mutants suggest that all six of the MCM subunits are required both during and after replication initiation [13]. However, in vitro, only a complex containing a double trimer of MCM4–MCM6–MCM7 has been shown to have weak helicase activity [14], which is inhibited by the addition of MCM2 [14]. A dimer of MCM3–MCM5 has also been reported to have inhibitory effects on the helicase activity of MCM4–MCM6–MCM7 in vitro [15]. The complexity of the DNA replication machinery in eukaryotes has led to a search for a simpler model. Such a model may be found in archaea.

Archaea as a model for DNA replication

Archaea are prokaryotic microbes that make up a third domain of life distinct from bacteria. Despite the fact that most archaea have genomes packaged as single circular chromosomes that are similar in size to those found in bacteria, it has been well established that their DNA replication proteins are much more similar to those found in eukaryotes than in prokaryotes [16]. The similarity between eukaryotic replication proteins and those found in archaea has led to a number of archaea being adopted as simplified model systems for studying eukaryotic DNA replication [17]. In most archaeal genomes sequenced to date, homologues of key eukaryotic replication proteins can be identified, including a single MCM homologue [18].

To date, the best-studied example of an archaeal MCM is from Methanothermobacter thermautotrophicus, which has a single MCM homologue. The structure of the N-terminal region of the M. thermautotrophicus MCM (MthMCM) has been solved, and shows that it forms a dodecameric complex, consisting of two hexamers stacked face to face [19]. The complex has a central channel large enough to accommodate dsDNA (double-stranded DNA) [19]. Studies using electron microscopy have also identified single hexameric and heptameric forms of MthMCM [2022]. It has been demonstrated in vitro that the MthMCM complex has DNA-dependent ATPase activity, can discriminate between dsDNA and ssDNA (single-stranded DNA) and has 3′→5′ helicase activity, which requires ATP hydrolysis [2327]. Homohexameric MCM complexes with similar biochemical activities have been identified in Sulfolobus solfataricus and Archaeoglobus fulgidis [28,29]. As in their eukaryotic counterparts, archaeal MCMs have three distinct domains: an N-terminal domain, a central ATPase, or catalytic domain, and a C-terminal domain. The N-terminal domain has been shown to be important in MCM multimerization and in binding to both ssDNA and dsDNA [12,25,30]. In vitro mutagenesis studies using the MthMCM complex have demonstrated that regions in both the N- and C-termini are important in coupling ATP hydrolysis to helicase activity [26]. In addition, it has been demonstrated recently that a conserved loop in the N-terminal region is involved in communication between the N terminus and the catalytic (ATPase) domain of the protein, supporting the fact that the N-terminal region is involved in modulating catalytic activity [31]. Also located in the N-terminal region of archaeal MCMs is a zinc-finger motif, which is conserved in MCM2, MCM4, MCM6 and MCM7 in eukaryotes [11]. Studies using the MthMCM revealed that the zinc finger is required for helicase activity [32].

Several motifs within the ATPase domain have been shown to be essential in the function of MCMs. These include the Walker A and B motifs and the arginine finger [SRF (Ser-Arg-Phe) motif], all of which are required for ATPase activity [23,24,27,33]. An insert in helix 2, which is conserved at the structural level and lies between the Walker A and B motifs, is essential for helicase activity [26]. Modelling of the position of the helix-2 insert within the MthMCM complex suggests that it protrudes into the central cavity and this has led to the hypothesis that it is physically involved in the separation of the DNA strands [26]. However, several alternative mechanisms for how MCMs separate dsDNA have also been suggested [34]. Although there is a large amount of data regarding the biochemical activity of archaeal MCMs in vitro, in vivo studies conducted have been limited to describing whether these proteins associate with other replication proteins [35]. There is currently no information available on the effects of mutations of MCMs in vivo. This is mainly due to the fact that many archaea, including M. thermautotrophicus in which much of the in vitro work has been carried out, are genetically intractable.

Methanococcus maripaludis: a genetically tractable model organism for studying DNA replication

M. maripaludis is a mesophilic methanogen, first isolated from salt marshes in North Carolina in the 1980s [36]. M. maripaludis is a strict anaerobe and is hydrogenotrophic, obtaining its energy from the reduction of carbon dioxide or acetate to methane, using hydrogen as the terminal electron acceptor. Cells are flagellated irregular cocci and have weak motility, an optimal growth temperature of 37°C and a doubling time of 2.3 h [36]. Cells can be grown to exponential phase overnight in defined liquid medium, and single colonies are visible after 3 days of growth on solid medium [37]. More recently, methods have been developed to allow large-scale growth of M. maripaludis in either batch or continuous culture [38].

In addition to the relative ease of growth of M. maripaludis in the laboratory, there is also a well-developed genetic system for the manipulation of this organism. An efficient poly(ethylene glycol) transformation method has been developed [39] and used effectively in numerous genetic studies in M. maripaludis [40,41]. A self-replicating vector (pDLT44), based on the plasmid pURB500 plus a puromycin-resistance gene, was the first shuttle vector developed for M. maripaludis [42]. Subsequently, an expression vector based on pURB500 with a histone promoter and ribosome-binding site from Methanococcus voltae was generated to allow the overexpression of recombinant genes in M. maripaludis [43]. The reporter gene lacZ was one of the first to be overexpressed in M. maripaludis, and the classic lacZ assay has since been optimized for use in M. maripaludis [41,43]. The base analogues 8-azahypoxanthine and 6-azauracil, which have bacteriocidal effects in M. maripaludis, have been established for use in counter selection. Currently, only two antibiotic markers are available for use in M. maripaludis. These are puromycin and neomycin. However, the development of a markerless mutagenesis strategy allows multiple mutations to be integrated into the genome using the same markers [44]. Extensive studies of the nitrogen fixation (nif) genes in M. maripaludis have shown that the nif promoter is tightly regulated and can be manipulated by changes in the nitrogen source in growth media. Growth in the presence of ammonia causes complete shut-off of the nif promoter, whereas growth with dinitrogen as the sole nitrogen source leads to strong expression from the nif promoter. The addition of alanine as a nitrogen source gives an intermediate level of expression [45]. The controllable nif promoter has been isolated and was used recently in experiments to repress the expression of genes involved in flagella assembly and function in M. maripaludis [46]. The relative ease of growth of this organism in the laboratory and the availability of genetic tools mean that M. maripaludis is potentially useful as a model for studying DNA replication in archaea.

Replication homologues in M. maripaludis

The genome sequence for M. maripaludis strain S2 [47] revealed that, when compared with most other archaea, M. maripaludis has some unusual features with respect to DNA replication. Although the genome of M. maripaludis contains homologues with most of the eukaryotic DNA replication proteins seen in other archaea, as well as some bacterial homologues (Table 1), there is no obvious Cdc6/Orc1 homologue. In contrast, all other archaea outside the Methanococci have at least one, and often two or more Cdc6/Orc1 homologues. Perhaps most interestingly, M. maripaludis has four MCM homologues as opposed to the single homologue found in most other archaea. The Methanocaldococcus jannaschii genome also contains four MCM homologues. However, one of these is found on an extrachromosomal element and has multiple mutations in the essential Walker A and B motifs, and is therefore presumed to be non-functional [48]. Furthermore, only one of the three chromosomal MCM homologues in M. jannaschii has the conserved zinc-finger motif [11], which has been shown to be important in DNA binding and is essential for helicase activity in MthMCM [32]. A few other archaeal species, including Methanopyrus kandleri and Methanosarcina acetivorans also possess multiple MCMs. However, closer examination of sequences of MCM proteins from these species reveals that there is only one MCM with the conserved functional domains required for activity [48,49]. In contrast, multiple sequence alignments show that all four M. maripaludis MCMs possess the conserved motifs required for function, including a zinc-finger domain, Walker A and B motifs, an arginine finger motif and an insert within helix 2 of the protein (Figure 1).

Table 1
Replication protein homologues in M. maripaludis S2

FEN1, flap structure-specific endonuclease 1; RPA, replication protein A.

ORF number Protein Eukaryotic/bacterial Function 
MMP0030 MCM Eukaryotic Replicative helicase? 
MMP0470 MCM Eukaryotic Replicative helicase? 
MMP0748 MCM Eukaryotic Replicative helicase? 
MMP1024 MCM Eukaryotic Replicative helicase? 
MMP0956 Topoisomerase I Prokaryotic DNA unwinding 
MMP0380 B-family DNA polymerase Eukaryotic DNA polymerization 
MMP1710 GINS15 Eukaryotic Polymerase recruitment 
MMP1126 Processivity factor (PCNA?) Eukaryotic Long-range DNA polymerization 
MMP1711 Processivity factor (PCNA?) Eukaryotic Long-range DNA polymerization 
MMP0032 Clamp loader Eukaryotic Binds and loads processivity factors 
MMP0427 Clamp loader Eukaryotic Binds and loads processivity factors 
MMP1032 RPA Eukaryotic ssDNA binding 
MMP0122 RPA? Eukaryotic ssDNA binding 
MMP0616 RPA? Eukaryotic ssDNA binding 
MMP0071 Primase, p48 Eukaryotic Adds primers to lagging strand 
MMP1286 Primase (DnaG homologue) Bacterial Adds primers to lagging strand 
MMP1313 FEN1/Rad2 Eukaryotic Removes primers from lagging strand 
MMP1374 RNaseHII Bacterial Removes primers from lagging strand 
MMP0837 RNaseHI Bacterial  
MMP0970 DNA ligase I Eukaryotic Ligation of Okazaki fragments 
MMP1397 Smc Eukaryotic Chromosome condensation and segregation 
MMP0989/1437 Type II topoisomerase (two subunits) Archaeal Decatenates chromosomes 
MMP0472 XerC Bacterial Decatenates chromosomes 
MMP0743 XerD Bacterial Decatenates chromosomes 
MMP0704/0593 ParA/ParB Bacterial Plasmid partitioning 
MMP1710 GINS15 Eukaryotic Polymerase recruitment 
ORF number Protein Eukaryotic/bacterial Function 
MMP0030 MCM Eukaryotic Replicative helicase? 
MMP0470 MCM Eukaryotic Replicative helicase? 
MMP0748 MCM Eukaryotic Replicative helicase? 
MMP1024 MCM Eukaryotic Replicative helicase? 
MMP0956 Topoisomerase I Prokaryotic DNA unwinding 
MMP0380 B-family DNA polymerase Eukaryotic DNA polymerization 
MMP1710 GINS15 Eukaryotic Polymerase recruitment 
MMP1126 Processivity factor (PCNA?) Eukaryotic Long-range DNA polymerization 
MMP1711 Processivity factor (PCNA?) Eukaryotic Long-range DNA polymerization 
MMP0032 Clamp loader Eukaryotic Binds and loads processivity factors 
MMP0427 Clamp loader Eukaryotic Binds and loads processivity factors 
MMP1032 RPA Eukaryotic ssDNA binding 
MMP0122 RPA? Eukaryotic ssDNA binding 
MMP0616 RPA? Eukaryotic ssDNA binding 
MMP0071 Primase, p48 Eukaryotic Adds primers to lagging strand 
MMP1286 Primase (DnaG homologue) Bacterial Adds primers to lagging strand 
MMP1313 FEN1/Rad2 Eukaryotic Removes primers from lagging strand 
MMP1374 RNaseHII Bacterial Removes primers from lagging strand 
MMP0837 RNaseHI Bacterial  
MMP0970 DNA ligase I Eukaryotic Ligation of Okazaki fragments 
MMP1397 Smc Eukaryotic Chromosome condensation and segregation 
MMP0989/1437 Type II topoisomerase (two subunits) Archaeal Decatenates chromosomes 
MMP0472 XerC Bacterial Decatenates chromosomes 
MMP0743 XerD Bacterial Decatenates chromosomes 
MMP0704/0593 ParA/ParB Bacterial Plasmid partitioning 
MMP1710 GINS15 Eukaryotic Polymerase recruitment 

ClustalX alignment of MCM sequences from M. maripaludis S2

Figure 1
ClustalX alignment of MCM sequences from M. maripaludis S2

All four sequences contain all of the motifs identified to date that are required for MCM function (annotated boxes). MMP0030, MMP0470 and MMP748 sequences are highly related. MMP1024 shows a slightly unusual zinc-finger motif (labelled 1), which is observed in some eukaryotic MCM sequences. MMP1024 also possesses a number of insertions compared with the other M. maripaludis MCMs (labelled 2–5 and discussed in the text).

Figure 1
ClustalX alignment of MCM sequences from M. maripaludis S2

All four sequences contain all of the motifs identified to date that are required for MCM function (annotated boxes). MMP0030, MMP0470 and MMP748 sequences are highly related. MMP1024 shows a slightly unusual zinc-finger motif (labelled 1), which is observed in some eukaryotic MCM sequences. MMP1024 also possesses a number of insertions compared with the other M. maripaludis MCMs (labelled 2–5 and discussed in the text).

Our initial sequence analysis indicates that three of the four M. maripaludis MCMs [ORFs (open reading frames) MMP0030, MMP0470 and MMP0748] are very similar to one another, whereas the fourth MCM (ORF MMP1024) is somewhat different and possesses several inserts. Three of these inserts are three to five amino acids long and occur towards the middle of the protein, whereas a larger insert (20 amino acids) followed by a smaller insert (five amino acids) are found towards the C-terminus (Figure 1). Proteomics data suggest that MMP0030, MMP0470 and MMP1024 are all expressed in M. maripaludis. Quantitative multidimensional capillary HPLC followed by quadropole ion-trap MS was used to separate and identify peptides from the whole M. maripaludis proteome [50]. Peptides were identified for MMP0030, MMP0470 and MMP1024 from cells grown in nitrogen-free medium. No peptides were detected for MMP0748. Thus existing proteomics data confirm that at least three of the four MCMs, MMP0030, MMP0470 and MMP1024, are normally expressed. Whether MMP0748 is expressed remains unclear.

The presence of multiple MCM homologues that are likely to be functional in M. maripaludis raises some interesting questions. For example, are all four of these proteins essential, as is found with MCM2–MCM7 in eukaryotes [13]? Do these proteins form an active heteromeric complex or many separate homohexamers? Data from M. jannaschii suggest that the MCM complex comprises either a heterohexamer containing three proteins (but requiring only one protein with a zinc finger), or a single homohexamer with the other MCM homologues being either non-functional or playing other roles. Whether additional MCM homologues are non-functional or being used for other functions, the question remains as to whether this is an ancient or recent duplication of MCMs within Methanococcus and why it is not seen in other archaea. The growing number of complete Methanococci genome sequences available (there are currently seven) and the availability of genetic tools for M. maripaludis means that we can begin to address these questions using a combination of in silico, in vitro and in vivo approaches. The M. maripaludis system provides an interesting system for the in vivo characterization of MCM proteins in replication and proliferation in the archaea. If multiple MCMs are found to be functional in this organism, M. maripaludis may provide a very interesting intermediate model for elucidating the functions of eukaryotic MCM2–MCM7.

Funding

A.D.W. is supported by a Biotechnology And Biological Sciences Research Council Ph.D. Studentship. Work in the laboratory is supported by the Biotechnology and Biological Sciences Research Council [grant number BB/F003099/1] and Cancer Research UK [grant number C23949/A7771] to J.P.J.C.

Molecular Biology of Archaea: Biochemical Society Focused Meeting held at University of St Andrews, U.K., 19–21 August 2008. Organized and Edited by Stephen Bell (Oxford, U.K.) and Malcolm White (St Andrews, U.K.).

Abbreviations

     
  • Cdc6

    cell division cycle 6

  •  
  • dsDNA

    double-stranded DNA

  •  
  • MCM

    minichromosome maintenance

  •  
  • MthMCM

    Methanothermobacter thermautotrophicus MCM

  •  
  • nif

    nitrogen fixation

  •  
  • ORC

    origin recognition complex

  •  
  • ORF

    open reading frame

  •  
  • ssDNA

    single-stranded DNA

  •  
  • STAT1

    signal transducer and activator of transcription 1

References

References
1
Blow
J.J.
Laskey
R.A.
A role for the nuclear envelope in controlling DNA replication within the cell cycle
Nature
1988
, vol. 
332
 (pg. 
546
-
548
)
2
Bell
S.P.
Mitchell
J.
Leber
J.
Kobayashi
R.
Stillman
B.
The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing
Cell
1995
, vol. 
83
 (pg. 
563
-
568
)
3
Shin
J.H.
Grabowski
B.
Kasiviswanathan
R.
Bell
S.D.
Kelman
Z.
Regulation of minichromosome maintenance helicase activity by Cdc6
J. Biol. Chem.
2003
, vol. 
278
 (pg. 
38059
-
38067
)
4
Maine
G.T.
Sinha
P.
Tye
B.K.
Mutants of S. cerevisiae defective in the maintenance of minichromosomes
Genetics
1984
, vol. 
106
 (pg. 
365
-
385
)
5
Chong
J.P.
Thommes
P.
Blow
J.J.
The role of MCM/P1 proteins in the licensing of DNA replication
Trends Biochem. Sci.
1996
, vol. 
21
 (pg. 
102
-
106
)
6
Snyder
M.
He
W.
Zhang
J.J.
The DNA replication factor MCM5 is essential for Stat1-mediated transcriptional activation
Proc. Natl. Acad. Sci. U.S.A.
2005
, vol. 
102
 (pg. 
14539
-
14544
)
7
Cortez
D.
Glick
G.
Elledge
S.J.
Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases
Proc. Natl. Acad. Sci. U.S.A.
2004
, vol. 
101
 (pg. 
10078
-
10083
)
8
Freeman
A.
Morris
L.S.
Mills
A.D.
Stoeber
K.
Laskey
R.A.
Williams
G.H.
Coleman
N.
Minichromosome maintenance proteins as biological markers of dysplasia and malignancy
Clin. Cancer Res.
1999
, vol. 
5
 (pg. 
2121
-
2132
)
9
Tan
D.F.
Huberman
J.A.
Hyland
A.
Loewen
G.M.
Brooks
J.S.
Beck
A.F.
Todorov
I.T.
Bepler
G.
MCM2: a promising marker for premalignant lesions of the lung: a cohort study
BMC Cancer
2001
, vol. 
1
 pg. 
6
 
10
Walters
A.D.
Chong
J.P.J.
Cox
L.
Drug targets in DNA replication
Molecular Themes in Eukaryotic DNA Replication
2009
Cambridge
Royal Society of Chemistry
 
in the press
11
Tye
B.K.
MCM proteins in DNA replication
Annu. Rev. Biochem.
1999
, vol. 
68
 (pg. 
649
-
686
)
12
Costa
A.
Onesti
S.
The MCM complex: (just) a replicative helicase?
Biochem. Soc. Trans.
2008
, vol. 
36
 (pg. 
136
-
140
)
13
Labib
K.
Tercero
J.A.
Diffley
J.F.
Uninterrupted MCM2–7 function required for DNA replication fork progression
Science
2000
, vol. 
288
 (pg. 
1643
-
1647
)
14
Ishimi
Y.
A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex
J. Biol. Chem.
1997
, vol. 
272
 (pg. 
24508
-
24513
)
15
Lee
J.K.
Hurwitz
J.
Isolation and characterization of various complexes of the minichromosome maintenance proteins of Schizosaccharomyces pombe
J. Biol. Chem.
2000
, vol. 
275
 (pg. 
18871
-
18878
)
16
Edgell
D.R.
Doolittle
W.F.
Archaea and the origin(s) of DNA replication proteins
Cell
1997
, vol. 
89
 (pg. 
995
-
998
)
17
Kelman
L.M.
Kelman
Z.
Archaea: an archetype for replication initiation studies?
Mol. Microbiol.
2003
, vol. 
48
 (pg. 
605
-
615
)
18
Majernik
A.I.
Jenkinson
E.R.
Chong
J.P.
DNA replication in thermophiles
Biochem. Soc. Trans.
2004
, vol. 
32
 (pg. 
236
-
239
)
19
Fletcher
R.J.
Bishop
B.E.
Leon
R.P.
Sclafani
R.A.
Ogata
C.M.
Chen
X.S.
The structure and function of MCM from archaeal M. thermoautotrophicum
Nat. Struct. Biol.
2003
, vol. 
10
 (pg. 
160
-
167
)
20
Yu
X.
VanLoock
M.S.
Poplawski
A.
Kelman
Z.
Xiang
T.
Tye
B.K.
Egelman
E.H.
The Methanobacterium thermoautotrophicum MCM protein can form heptameric rings
EMBO Rep.
2002
, vol. 
3
 (pg. 
792
-
797
)
21
Pape
T.
Meka
H.
Chen
S.
Vicentini
G.
van Heel
M.
Onesti
S.
Hexameric ring structure of the full-length archaeal MCM protein complex
EMBO Rep.
2003
, vol. 
4
 (pg. 
1079
-
1083
)
22
Costa
A.
Pape
T.
van Heel
M.
Brick
P.
Patwardhan
A.
Onesti
S.
Structural studies of the archaeal MCM complex in different functional states
J. Struct. Biol.
2006
, vol. 
156
 (pg. 
210
-
219
)
23
Chong
J.P.
Hayashi
M.K.
Simon
M.N.
Xu
R.M.
Stillman
B.
A double-hexamer archaeal minichromosome maintenance protein is an ATP-dependent DNA helicase
Proc. Natl. Acad. Sci. U.S.A.
2000
, vol. 
97
 (pg. 
1530
-
1535
)
24
Kelman
Z.
Lee
J.K.
Hurwitz
J.
The single minichromosome maintenance protein of Methanobacterium thermoautotrophicum ΔH contains DNA helicase activity
Proc. Natl. Acad. Sci. U.S.A.
1999
, vol. 
96
 (pg. 
14783
-
14788
)
25
Kasiviswanathan
R.
Shin
J.H.
Melamud
E.
Kelman
Z.
Biochemical characterization of the Methanothermobacter thermautotrophicus minichromosome maintenance (MCM) helicase N-terminal domains
J. Biol. Chem.
2004
, vol. 
279
 (pg. 
28358
-
28366
)
26
Jenkinson
E.R.
Chong
J.P.
Minichromosome maintenance helicase activity is controlled by N- and C-terminal motifs and requires the ATPase domain helix-2 insert
Proc. Natl. Acad. Sci. U.S.A.
2006
, vol. 
103
 (pg. 
7613
-
7618
)
27
Shechter
D.F.
Ying
C.Y.
Gautier
J.
The intrinsic DNA helicase activity of Methanobacterium thermoautotrophicum ΔH minichromosome maintenance protein
J. Biol. Chem.
2000
, vol. 
275
 (pg. 
15049
-
15059
)
28
Carpentieri
F.
De Felice
M.
De Falco
M.
Rossi
M.
Pisani
F.M.
Physical and functional interaction between the minichromosome maintenance-like DNA helicase and the single-stranded DNA binding protein from the crenarchaeon Sulfolobus solfataricus
J. Biol. Chem.
2002
, vol. 
277
 (pg. 
12118
-
12127
)
29
Grainge
I.
Scaife
S.
Wigley
D.B.
Biochemical analysis of components of the pre-replication complex of Archaeoglobus fulgidus
Nucleic Acids Res.
2003
, vol. 
31
 (pg. 
4888
-
4898
)
30
McGeoch
A.T.
Trakselis
M.A.
Laskey
R.A.
Bell
S.D.
Organization of the archaeal MCM complex on DNA and implications for the helicase mechanism
Nat. Struct. Mol. Biol.
2005
, vol. 
12
 (pg. 
756
-
762
)
31
Sakakibara
N.
Kasiviswanathan
R.
Melamud
E.
Han
M.
Schwarz
F.P.
Kelman
Z.
Coupling of DNA binding and helicase activity is mediated by a conserved loop in the MCM protein
Nucleic Acids Res.
2008
, vol. 
36
 (pg. 
1309
-
1320
)
32
Poplawski
A.
Grabowski
B.
Long
S.E.
Kelman
Z.
The zinc finger domain of the archaeal minichromosome maintenance protein is required for helicase activity
J. Biol. Chem.
2001
, vol. 
276
 (pg. 
49371
-
49377
)
33
Davey
M.J.
Indiani
C.
O'Donnell
M.
Reconstitution of the Mcm2–7p heterohexamer, subunit arrangement, and ATP site architecture
J. Biol. Chem.
2003
, vol. 
278
 (pg. 
4491
-
4499
)
34
Takahashi
T.S.
Wigley
D.B.
Walter
J.C.
Pumps, paradoxes and ploughshares: mechanism of the MCM2–7 DNA helicase
Trends Biochem. Sci.
2005
, vol. 
30
 (pg. 
437
-
444
)
35
Myllykallio
H.
Lopez
P.
Lopez-Garcia
P.
Heilig
R.
Saurin
W.
Zivanovic
Y.
Philippe
H.
Forterre
P.
Bacterial mode of replication with eukaryotic-like machinery in a hyperthermophilic archaeon
Science
2000
, vol. 
288
 (pg. 
2212
-
2215
)
36
Jones
W.J.
Paynter
M.J.B.
Gupta
R.
Characterization of Methanococcus maripaludis sp. nov., a new methanogen isolated from salt marsh sediment
Archaeal Microbiol.
1983
, vol. 
135
 (pg. 
91
-
95
)
37
Jones
W.J.
Whitman
W.B.
Fields
R.D.
Wolfe
R.S.
Growth and plating efficiency of Methanococci on agar media
Appl. Environ. Microbiol.
1983
, vol. 
46
 (pg. 
220
-
226
)
38
Haydock
A.K.
Porat
I.
Whitman
W.B.
Leigh
J.A.
Continuous culture of Methanococcus maripaludis under defined nutrient conditions
FEMS Microbiol. Lett.
2004
, vol. 
238
 (pg. 
85
-
91
)
39
Tumbula
D.
Mkaula
R.
Whitan
W.B.
Transformation of Methanococcus maripaludis and identification of PstI-like restriction enzymes
FEMS Microbiol. Lett.
1994
, vol. 
121
 (pg. 
309
-
314
)
40
Dodsworth
J.A.
Cady
N.C.
Leigh
J.A.
2-Oxoglutarate and the PII homologues NifI1 and NifI2 regulate nitrogenase activity in cell extracts of Methanococcus maripaludis
Mol. Microbiol.
2005
, vol. 
56
 (pg. 
1527
-
1538
)
41
Lie
T.J.
Leigh
J.A.
Genetic screen for regulatory mutations in Methanococcus maripaludis and its use in identification of induction-deficient mutants of the euryarchaeal repressor NrpR
Appl. Environ. Microbiol.
2007
, vol. 
73
 (pg. 
6595
-
6600
)
42
Tumbula
D.L.
Bowen
T.L.
Whitman
W.B.
Characterization of pURB500 from the archaeon Methanococcus maripaludis and construction of a shuttle vector
J. Bacteriol.
1997
, vol. 
179
 (pg. 
2976
-
2986
)
43
Gardner
W.L.
Whitman
W.B.
Expression vectors for Methanococcus maripaludis: overexpression of acetohydroxyacid synthase and β-galactosidase
Genetics
1999
, vol. 
152
 (pg. 
1439
-
1447
)
44
Moore
B.C.
Leigh
J.A.
Markerless mutagenesis in Methanococcus maripaludis demonstrates roles for alanine dehydrogenase, alanine racemase, and alanine permease
J. Bacteriol.
2005
, vol. 
187
 (pg. 
972
-
979
)
45
Lie
T.J.
Leigh
J.A.
Regulatory response of Methanococcus maripaludis to alanine, an intermediate nitrogen source
J. Bacteriol.
2002
, vol. 
184
 (pg. 
5301
-
5306
)
46
Chaban
B.
Ng
S.Y.
Kanbe
M.
Saltzman
I.
Nimmo
G.
Aizawa
S.
Jarrell
K.F.
Systematic deletion analyses of the fla genes in the flagella operon identify several genes essential for proper assembly and function of flagella in the archaeon, Methanococcus maripaludis
Mol. Microbiol.
2007
, vol. 
66
 (pg. 
596
-
609
)
47
Hendrickson
E.L.
Kaul
R.
Zhou
Y.
Bovee
D.
Chapman
P.
Chung
J.
Conway de Macario
E.
Dodsworth
J.A.
Gillett
W.
Graham
D.E.
, et al. 
Complete genome sequence of the genetically tractable hydrogenotrophic methanogen Methanococcus maripaludis
J. Bacteriol.
2004
, vol. 
186
 (pg. 
6956
-
6969
)
48
McGeoch
A.T.
Bell
S.D.
Extra-chromosomal elements and the evolution of cellular DNA replication machineries
Nat. Rev. Mol. Cell Biol.
2008
, vol. 
9
 (pg. 
569
-
574
)
49
Jenkinson
E.R.
Chong
J.P.
Initiation of archaeal DNA replication
Biochem. Soc. Trans.
2003
, vol. 
31
 (pg. 
669
-
673
)
50
Xia
Q.
Hendrickson
E.L.
Zhang
Y.
Wang
T.
Taub
F.
Moore
B.C.
Porat
I.
Whitman
W.B.
Hackett
M.
Leigh
J.A.
Quantitative proteomics of the archaeon Methanococcus maripaludis validated by microarray analysis and real time PCR
Mol. Cell. Proteomics
2006
, vol. 
5
 (pg. 
868
-
881
)