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PubMed2006

Controlling of physicochemical properties of nickel-substituted MCM-41 by adjustment of the synthesis solution pH and tetramethylammonium silicate concentration.

The effect of initial synthesis solution pH and tetramethylammonium silicate concentration in the synthesis solution on the physical and chemical properties of MCM-41 was systematically investigated using N(2) physisorption, X-ray diffraction, temperature-programmed reduction, in situ Fourier transform IR, UV-vis, and X-ray absorption spectroscopies. pH and tetramethylammonium (TMA) fraction affect the porosity of MCM-41 and the reducibility of incorporated Ni cations; higher pH and TMA concentration produced more porosity with higher stability against reduction, which is attributed to more metal ions locating in the interior of the silica walls. The control of the pore diameter of mesoporous MCM-41 at the sub-nanometer scale may be accomplished by adjusting the pH and TMA fraction. pH may be used to control the surface free silanol group density and nickel reduction degree as well, and this is useful in the design of a specific catalyst for particular reactions, such as CO methanation, which requires highly dispersed, stable metallic clusters with controllable size.

Journal Article↗
PubMed2005

Entrapment of organic solutes by the water cage in the nanochannel of MCM-41.

The effect of MCM-41 on the ESR spectrum of an aqueous spin probe solution was observed. The sharp ESR spectrum turns into a rather broad characteristic one leaving a sharper signal as the minor component, immediately after the addition of MCM-41 powder to the system. This observation indicates that MCM-41 traps the solute molecule into the nanochannel by letting the solvent water form a rather stable molecular cage, since the ESR line shape indicates that the nitroxide radical undergoes anisotropic rotation without being adsorbed on the wall. Thermodynamic parameters for this process are estimated from the temperature dependencies of the trapping efficiency. This process is explained in terms of the surface enthalpy of the liquid specifically intensified in the nanospace.

Journal Article↗
PubMed2006

n- and isoalkane adsorption mechanisms on zeolite MCM-22.

Low-coverage adsorption properties (Henry constants, adsorption enthalpy, and entropy) of linear and branched alkanes (C3-C8) on zeolite MCM-22 were determined using the chromatographic technique at temperatures between 420 and 540 K. It was found that adsorption enthalpy and entropy of linear alkanes vary in a nonmonotonic way with carbon number. The adsorption behavior of alkanes was rationalized on the basis of the pore geometry. Short molecules prefer to reside in the pockets of the MCM-22 supercage, where they maximize energetic interaction with the zeolite. Longer molecules reside in the larger central part of the supercage. For carbon numbers up to six, singly branched alkanes are selectively adsorbed over their linear counterparts. This preference originates from the entropic advantage of singly branched molecules inside MCM-22 supercages, where these species have high rotational freedom because of their small length.

Adsorption↗
PubMed2006

MCM-41 supported Cu-Mn catalysts for catalytic oxidation of toluene at low temperatures.

Complete catalytic oxidation of toluene was investigated on Cu-Mn doped mesoporous and microporous catalysts, i.e., Cu-Mn/MCM-41, Cu-Mn/beta-zeolite, Cu-Mn/ZSM-5 (where SiO2/Al2O3 is either 25 or 38), and Cu-Mn/porous silica, in the presence of excess oxygen. The result shows that mesoporous catalysts have exhibited the highest catalytic activity among these catalysts above. The less amount of coke formation due to the unique mesoporous structures could play a key role in the high activity on the mesoporous catalyst. In addition, the bimetallic Cu-Mn-MCM-41 supported catalyst shows higher oxidation activity than either single metal catalyst, i.e., Cu-MCM-41 and Mn-MCM-41. The highly dispersed Cu-Mn mixed oxides on mesoporous structures probably provide active sites for the complete oxidation of toluene on these mesoporous catalysts.

Journal Article↗
PubMed2006

Adsorption of simple gases in MCM-41 materials: the role of surface roughness.

This paper reports the development and testing of atomistic models of silica MCM-41 pores. Model A is a regular cylindrical pore having a constant section. Model B has a surface disorder that reproduces the morphological features of a pore obtained from an on-lattice simulation that mimics the synthesis process of MCM-41 materials. Both models are generated using a similar procedure, which consists of carving the pore out of an atomistic silica block. The differences between the two models are analyzed in terms of small angle neutron scattering spectra as well as adsorption isotherms and isosteric heat curves for Ar at 87 K and Xe at 195 K. As expected for capillary condensation in regular nanopores, the Ar and Xe adsorption/desorption cycles for model A exhibit a large hysteresis loop having a symmetrical shape, i.e., with parallel adsorption and desorption branches. The features of the adsorption isotherms for model B strongly depart from those observed for model A. Both the Ar and Xe adsorption branches for model B correspond to a quasicontinuous pore filling that involves coexistence within the pore of liquid bridges and gas nanobubbles. As in the case of model A, the Ar adsorption isotherm for model B exhibits a significant hysteresis loop; however, the shape of the loop is asymmetrical with a desorption branch much steeper than the adsorption branch. In contrast, the adsorption/desorption cycle for Xe in model B is quasicontinuous and quasireversible. Comparison with adsorption and neutron scattering experiments suggests that model B is too rough at the molecular scale but reproduces reasonably the surface disorder of real MCM-41 at larger length scales. In contrast, model A is smooth at small length scales in agreement with experiments but seems to be too ordered at larger length scales.

Journal Article↗
PubMed2006

GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks.

The components of the replisome that preserve genomic stability by controlling the progression of eukaryotic DNA replication forks are poorly understood. Here, we show that the GINS (go ichi ni san) complex allows the MCM (minichromosome maintenance) helicase to interact with key regulatory proteins in large replisome progression complexes (RPCs) that are assembled during initiation and disassembled at the end of S phase. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I. During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs.

Cell Cycle Proteins↗
PubMed2003

Human cytomegalovirus prevents replication licensing by inhibiting MCM loading onto chromatin.

To allow DNA replication only once per cell cycle, origins of replication are reactivated ('licensed') during each G1 phase. Licensing is facilitated by assembly of the pre-replicative complex (pre-RC) at origins that concludes with loading the mini-chromosome maintenance (MCM) complex onto chromatin. Here we show that a virus exploits pre-RC assembly to selectively inhibit cellular DNA replication. Infection of quiescent primary fibroblasts with human cytomegalovirus (HCMV) induces all pre-RC factors. Although this is sufficient to assemble the MCM-loading factors onto chromatin, as it is in serum-stimulated cells, the virus inhibits loading of the MCM complex itself, thereby prematurely abrogating replication licensing. This provides a new level of control in pre-RC assembly and a mechanistic rationale for the unusual HCMV-induced G1 arrest that occurs despite the activation of the cyclin E-dependent transcription programme. Thus, this particularly large virus might thereby secure the supply with essential replication factors but omit competitive cellular DNA replication.

Animals↗
PubMed2002

Synthesis of nopol over MCM-41 catalysts.

MCM-41 was found to be an active heterogeneous catalyst for the synthesis of nopol by the Prins condensation of beta-pinene and paraformaldehyde, but Sn-MCM-41 in which Sn has been grafted on MCM-41 by chemical vapor deposition is far more active and combines high efficiency and recyclability.

Journal Article↗
PubMed2003

Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix.

Minichromosome maintenance proteins (Mcm) 2-7 play essential roles in eukaryotic DNA replication. Several reports have indicated the usefulness of Mcm proteins as markers of cancer cells in histopathological diagnosis. However, their mode of expression and pathophysiological significance in cancer cells remain to be clarified. We compared the level of expression of Mcm proteins among human HeLa uterine cervical carcinoma cells, SV40-transformed human fibroblast GM00637 cells and normal human fibroblast WI-38 cells. All the proteins examined were detected in HeLa and GM cells at 6-10 times the level found in WI-38 cells on average. This increase was observed both in total cellular proteins and in the chromatin-bound fraction. Consistently, Mcm2 mRNA was enriched in HeLa cells to approximately four times the level in WI-38 cells, and the synthesis of Mcm4, 6 and 7 proteins was accelerated in HeLa cells. Immunohistochemical studies of surgical materials from human uterine cervix showed that Mcm3 and 4 are ubiquitously expressed in cancer cells. Further, the positive rate and level of Mcm3 and 4 expression appeared to be higher in cancer cells than in normal proliferating cells of the uterine cervix and dysplastic cells, suggesting that they can be useful markers to distinguish these cells.

Animals↗
PubMed1996

hCDC47, a human member of the MCM family. Dissociation of the nucleus-bound form during S phase.

hCDC47 is a putative human homologue of yeast CDC47 and a member of the MCM protein family, which has been implicated in the regulatory machinery causing DNA to replicate only once in the S phase. In the present study, we performed an initial characterization of hCDC47. We found that hCDC47 protein was present in the nucleus of cultured human cells in two different forms; one extractable by a non-ionic detergent and the other resistant to such extraction and tightly associated with the nucleus. The levels of the nucleus-bound form gradually diminished during S phase progression, although the total amount of nuclear hCDC47 protein remained relatively constant, suggesting that the nucleus-bound form becomes dissociated from the nuclear structure during DNA replication. This behavior of hCDC47 protein is very similar to that of other mammalian MCM proteins reported recently. We also found that expression of hCDC47 mRNA was repressed in quiescent cells but was induced at the late G1 to S phase by growth factor stimulation. Together, these findings indicate that hCDC47 protein together with other MCM proteins participates in the regulation of mammalian DNA replication.

Cell Cycle↗
PubMed1997

In vivo interaction of human MCM heterohexameric complexes with chromatin. Possible involvement of ATP.

The MCM protein family, which consists of at least six members, has been implicated in the regulatory machinery causing DNA to replicate once in the S phase. Mammalian MCM proteins are present in the nucleus in two different forms, one extractable by nonionic detergents and the other resistant to such extraction. The latter is assumed to be tightly associated with nuclear structures and released at the time of initiation of replication. However, details of the mode of binding remain unclear. In the present study, we found that, in nonionic detergent-permeabilized nuclei, the association of human MCM (hMCM) proteins with them could be stabilized by the addition of ATP. The hMCMs bound to the nuclei in the presence of ATP were released by digestion with nucleases, suggesting that they are chromatin-associated. The nuclease-directed solubilization of the chromatin-bound hMCMs thus provided a means to analyze them as well as soluble hMCMs by co-immunoprecipitation. The results indicate that the six hMCM members exist as heterocomplexes, whether bound or unbound. We therefore propose that hMCM proteins may function in DNA replication as heterohexamers associated with chromatin and that ATP is possibly involved in the association. Nuclease digestion-immunoprecipitation techniques of the type described here should facilitate further elucidation of the mode of interaction between hMCMs and chromatin.

Adenosine Triphosphate↗
PubMed2003

Evidence for a role of MCM (mini-chromosome maintenance)5 in transcriptional repression of sub-telomeric and Ty-proximal genes in Saccharomyces cerevisiae.

The MCM (mini-chromosome maintenance) genes have a well established role in the initiation of DNA replication and in the elongation of replication forks in Saccharomyces cerevisiae. In this study we demonstrate elevated expression of sub-telomeric and Ty retrotransposon-proximal genes in two mcm5 strains. This pattern of up-regulated genes resembles the genome-wide association of MCM proteins to chromatin that was reported earlier. We link the altered gene expression in mcm5 strains to a reversal of telomere position effect (TPE) and to remodeling of sub-telomeric and Ty chromatin. We also show a suppression of the Ts phenotype of a mcm5 strain by the high copy expression of the TRA1 component of the chromatin-remodeling SAGA/ADA (SPT-ADA-GCN5 acetylase/ADAptor). We propose that MCM proteins mediate the establishment of silent chromatin domains around telomeres and Ty retrotransposons.

Blotting, Northern↗
PubMed1998

Association of RPA with chromosomal replication origins requires an Mcm protein, and is regulated by Rad53, and cyclin- and Dbf4-dependent kinases.

Eukaryotic cells use multiple replication origins to replicate their large genomes. Some origins fire early during S phase whereas others fire late. In Saccharomyces cerevisiae, initiator sequences (ARSs) are bound by the origin recognition complex (ORC). Cdc6p synthesized at the end of mitosis joins ORC and facilitates recruitment of Mcm proteins, which renders origins competent to fire. However, origins fire only upon the subsequent activation of S phase cyclin-dependent kinases (S-CDKs) and Dbf4/Cdc7 at the G1/S boundary. We have used a chromatin immunoprecipitation assay to measure the association with ARS sequences of DNA primase and the single-stranded DNA binding replication protein A (RPA) when fork movement is inhibited by hydroxyurea (HU). RPA's association with origins requires S-CDKs, Dbf4/Cdc7 kinase and an Mcm protein. The recruitment of DNA primase depends on RPA. Furthermore, early- and late-firing origins differ not in the timing of their recruitment of an Mcm protein, but in the timing of RPA's recruitment. RPA is recruited to early but not to late origins in HU. We also show that Rad53 kinase is required to prevent RPA association with a late origin in HU. Our data suggest that the origin unwinding accompanied by RPA association is a key step, regulated by S-CDKs, Dbf4/Cdc7 and Rad53p. Thus, in the presence of active S-CDKs and Dbf4/Cdc7, Mcms may open origins and thereby facilitate the loading of RPA.

Adenosine Triphosphatases↗
PubMed2003

Multiple ORC-binding sites are required for efficient MCM loading and origin firing in fission yeast.

In most eukaryotes, replication origins are composed of long chromosome regions, and the exact sequences required for origin recognition complex (ORC) and minichromosome maintenance (MCM) complex association remain elusive. Here, we show that two stretches of adenine/thymine residues are collectively essential for a fission yeast chromosomal origin. Chromatin immunoprecipitation assays revealed that the ORC subunits are located within a 1 kb region of ori2004. Analyses of deletion derivatives of ori2004 showed that adenine stretches are required for ORC binding in vivo. Synergistic interaction between ORC and adenine stretches was observed. On the other hand, MCM subunits were localized preferentially to a region near the initiation site, which is distant from adenine stretches. This association was dependent on adenine stretches and stimulated by a non-adenine element. Our results suggest that association of multiple ORC molecules with a replication origin is required for efficient MCM loading and origin firing in fission yeast.

Adenine↗
PubMed1997

Mutational analysis of Cdc19p, a Schizosaccharomyces pombe MCM protein.

The cdc19+ gene encodes an essential member of the MCM family of replication proteins in Schizosaccharomyces pombe. We have examined the structure and function of the Cdc19p protein using molecular and genetic approaches. We find that overproduction of wild-type Cdc19p in wild-type cells has no effect, but cdc19-P1 mutant cells do not tolerate elevated levels of other MCM proteins or overexpression of mutant forms of Cdc19p. We have found genetic interactions between cdc19+ and genes encoding subunits of DNA polymerase delta and the replication initiator cdc18+. We have constructed a series of point mutations and sequence deletions throughout Cdc19p, which allow us to distinguish essential from nonessential regions of the protein. Not surprisingly, conserved residues in the MCM homology domain are required for protein function, but some residues outside the core homology domain are dispensable.

Animals↗
PubMed2003

Identification and functional characterization of a new member of the human Mcm protein family: hMcm8.

The six minichromosome maintenance proteins (Mcm2-7) are required for both the initiation and elongation of chromosomal DNA, ensuring that DNA replication takes place once, and only once, during the S phase. Here we report on the cloning of a new human Mcm gene (hMcm8) and on characterisation of its protein product. The hMcm8 gene contains the central Mcm domain conserved in the Mcm2-7 gene family, and is expressed in a range of cell lines and human tissues. hMcm8 mRNA accumulates during G(1)/S phase, while hMcm8 protein is detectable throughout the cell cycle. Immunoprecipitation-based studies did not reveal any participation of hMcm8 in the Mcm3/5 and Mcm2/4/6/7 subcomplexes. hMcm8 localises to the nucleus, although it is devoid of a nuclear localisation signal, suggesting that it binds to a nuclear protein. In the nucleus, the hMcm8 structure-bound fraction is detectable in S, but not in G(2)/M, phase, as for hMcm3. However, unlike hMcm3, the hMcm8 structure-bound fraction is not detectable in G(1) phase. Overall, our data identify a new Mcm protein, which does not form part of the Mcm2-7 complex and which is only structure-bound during S phase, thus suggesting its specific role in DNA replication.

Blotting, Western↗
PubMed2006

Structural basis of the Methanothermobacter thermautotrophicus MCM helicase activity.

The MCM complex from the archaeon Methanother-mobacter thermautotrophicus is a model for the eukaryotic MCM2-7 helicase. We present electron-microscopy single-particle reconstructions of a DNA treated M.thermautotrophicus MCM sample and a ADP.AlF(x) treated sample, respectively assembling as double hexamers and double heptamers. The electron-density maps display an unexpected asymmetry between the two rings, suggesting that large conformational changes can occur within the complex. The structure of the MCM N-terminal domain, as well as the AAA+ and the C-terminal HTH dom-ains of ZraR can be fitted into the reconstructions. Distinct configurations can be modelled for the AAA+ and the HTH domains, suggesting the nature of the conformational change within the complex. The pre-sensor 1 and the helix 2 insertions, important for the activity, can be located pointing towards the centre of the channel in the presence of DNA. We propose a mechanistic model for the helicase activity, based on a ligand-controlled rotation of the AAA+ subunits.

Adenosine Triphosphatases↗
PubMed2006

Stimulation of MCM helicase activity by a Cdc6 protein in the archaeon Thermoplasma acidophilum.

Replicative DNA helicases are ring-shaped hexamers that play an essential role in chromosomal DNA replication. They unwind the two strands of the duplex DNA and provide the single-stranded (ss) DNA substrate for the polymerase. The minichromosome maintenance (MCM) proteins are thought to function as the replicative helicases in eukarya and archaea. The proteins of only a few archaeal organisms have been studied and revealed that although all have similar amino acid sequences and overall structures they differ in their biochemical properties. In this report the biochemical properties of the MCM protein from the archaeon Thermoplasma acidophilum is described. The enzyme has weak helicase activity on a substrate containing only a 3'-ssDNA overhang region and the protein requires a forked DNA structure for efficient helicase activity. It was also found that the helicase activity is stimulated by one of the two T.acidophilum Cdc6 homologues. This is an interesting observation as it is in sharp contrast to observations made with MCM and Cdc6 homologues from other archaea in which the helicase activity is inhibited when bound to Cdc6.

Archaeal Proteins↗