The Saccharomyces cerevisiae Mcm1 protein is an essential multifunctional transcription factor which is highly homologous to human serum response factor. Mcm1 protein acts on a large number of distinctly regulated genes: haploid cell-type-specific genes, G2-cell-cycle-regulated genes, pheromone-induced genes, arginine metabolic genes, and genes important for cell wall and cell membrane function. We show here that Mcm1 protein is phosphorylated in vivo. Several (more than eight) isoforms of Mcm1 protein, resolved by isoelectric focusing, are present in vivo; two major phosphorylation sites lie in the N-terminal 17 amino acids immediately adjacent to the conserved MADS box DNA-binding domain. The implications of multiple species of Mcm1, particularly the notion that a unique Mcm1 isoform could be required for regulation of a specific set of Mcm1s target genes, are discussed. We also show here that Mcm1 plays an important role in the response to stress caused by NaCl. G. Yu, R. J. Deschenes, and ...

Molecular cloning and characterisation of a human nuclear protein designated BM28 is reported. On the amino acid level this 892 amino acid protein, migrating on SDS-gels as a 125 kDa polypeptide, shares areas of significant similarity with a recently defined family of early S phase proteins. The members of this family, the Saccharomyces cerevisiae Mcm2p, Mcm3p, Cdc46p/Mcm5p, the Schizosaccharomyces pombe Cdc21p and the mouse protein P1 are considered to be involved in the onset of DNA replication. The highest similarity was found with Mcm2p (42% identity over the whole length and higher than 75% over a conservative region of 215 amino acid residues), suggesting that BM28 could represent the human homologue of the S. cerevisiae MCM2. Using antibodies raised against the recombinant BM28 the corresponding antigen was found to be localised in the nuclei of various mammalian cells. Microinjection of anti-BM28 antibody into synchronised mouse NIH3T3 or human HeLa cells presents evidence for the ...

The replicative helicase in eukaryotic cells is comprised of minichromosome maintenance (Mcm) proteins 2 through 7 (Mcm2-7) and is a key target for regulation of cell proliferation. In addition, it is regulated in response to replicative stress. One of the protein kinases that targets Mcm2-7 is the Dbf4-dependent kinase Cdc7 (DDK). In a previous study, we showed that alanine mutations of the DDK phosphorylation sites at S164 and S170 in Saccharomyces cerevisiae Mcm2 result in sensitivity to caffeine and methyl methanesulfonate (MMS) leading us to suggest that DDK phosphorylation of Mcm2 is required in response to replicative stress. We show here that a strain with the mcm2 allele lacking DDK phosphorylation sites (mcm2AA) is also sensitive to the ribonucleotide reductase inhibitor, hydroxyurea (HU) and to the base analogue 5-fluorouracil (5-FU) but not the radiomimetic drug, phleomycin. We screened the budding yeast non-essential deletion collection for synthetic lethal interactions with mcm2AA and

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The exact duplication of a genome once per cell division is required of every proliferating cell. To achieve this goal, eukaryotes adopt a strategy that limits every replication origin to a single initiation event within a narrow window of the cell cycle by temporally separating the assembly of the pre-replication complex (pre-RC) from the initiation of DNA synthesis. A key component of the pre-RC is the hexameric MCM complex, which is also the presumed helicase of the growing forks. An elaborate mechanism recruits the MCM complex to replication origins, and a regulatory chain reaction converts the poised, but inactive, MCM complex into an enzymatically active helicase. A growing list of proteins, including Mcm10 and Cdt1, are involved in the recruitment process. Two protein kinases, the Cdc7-Dbf4 kinase (DDK) and the cyclin-dependent kinase (CDK), trigger a chain reaction that results in the phosphorylation of the MCM complex and finally in the initiation of DNA synthesis. A composite picture ...

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Minichromosome maintenance (MCM) proteins are essential for the initiation of DNA replication and have been found to be relevant markers for prognosis in a variety of tumours. The aim of this study was to assess the proliferative activity of diffuse large B-cell lymphoma (DLBCL) in tissue microarray (TMA) using one of the minichromosome maintenance proteins (Mcm2) and to explore its potential value to predict prognosis. Immunohistochemistry for Mcm2 was performed on TMAs constructed from 302 cases of DLBCL. A monoclonal mouse antibody was used after heat induced antigen retrieval. Mcm2 expression was scored quantitatively. Positivity for Mcm2 was defined as presence of nuclear expression of Mcm2 in greater than or equal to 40 % of tumour cells. A statistical analysis was carried out of the association of Mcm2 and the clinico-pathological characteristics. Mcm2 expression was clearly evident in the nuclei of proliferating non-neoplastic cells and tumour cells. Positivity for Mcm2 was found in 46% (98/211)

Numerous observations suggest that MCM association with chromatin is essential for DNA replication. The phenotype of mutations and the results of antibody injection and immunodepletion in yeasts, human cells, Xenopus, and Drosophila suggest a requirement for MCMs in DNA replication (for reviews see Tye, 1994; Chong et al., 1996). Importantly, work in Xenopus suggests that MCMs carry out their essential function when bound to chromatin; an MCM-containing complex can be experimentally induced to bind chromosomes and allow DNA replication in G2 nuclei that normally lack bound MCMs (Chong et al., 1995; Madine et al., 1995). Consistent with the idea that chromatin binding of MCMs is required for S phase, binding of MCMs to chromatin occurs before initiation of replication in mammalian cultured cells (Kimura et al., 1994) and in the Drosophila embryo (Su and OFarrell, 1997). We also found that MCM-chromosome association increased in response to cyclin E and that this increase preceded BrdU ...

The following sections contain reference sequences that belong to a specific genome build. Explain. This section includes genomic Reference Sequences (RefSeqs) from all assemblies on which this gene is annotated, such as RefSeqs for chromosomes and scaffolds (contigs) from both reference and alternate assemblies. Model RNAs and proteins are also reported here.. ...

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MCM Proteins Are Associated with RNA Polymerase II Holoenzyme: MCMs are a family of proteins related to ATP-dependent helicases that bind to origin recognition

Not all available origins of replication fire during a normal S-phase. But when replication is perturbed, otherwise dormant origins go to work, Woodward et al. show on page 673.. Cells initially respond to slowed replication by turning on the ATR-dependent checkpoint, which prevents other origins from firing and thus getting into trouble too. But if the cell decides it is time to recover from that checkpoint, the mechanism discovered by Woodward et al. may ensure that there are enough origins to get the job done.. The excess supply of origins arises from an excess of sites that have the minichromosome maintenance protein complexes, Mcm2-7. These complexes are loaded onto chromatin before S-phase and are required to license replication origins for use. However, the number of complexes loaded is much higher than the number normally used.. Working in Xenopus egg extract, Woodward et al. found that replication speed, origin spacing, and the slowing in response to the DNA polymerase inhibitor ...

Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. Assembly of these prereplicative complexes (pre-RCs) requires the Origin Recog …

The KOMP Repository is located at the University of California Davis and Childrens Hospital Oakland Research Institute. Question? Comments? For Mice, Cells, and germplasm please contact us at [email protected], US 1-888-KOMP-MICE or International +1-530-752-KOMP, or for vectors [email protected] or +1-510-450-7917 ...

Complete information for MCM10 gene (Protein Coding), Minichromosome Maintenance 10 Replication Initiation Factor, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

Eukaryotic cells license each DNA replication origin during G1 phase by assembling a prereplication complex that contains a Mcm2-7 (minichromosome maintenance proteins 2-7) double hexamer. During S phase, each Mcm2-7 hexamer forms the core of a replicative DNA helicase. However, the mechanisms of origin licensing and helicase activation are poorly understood. The helicase loaders ORC-Cdc6 function to recruit a single Cdt1-Mcm2-7 heptamer to replication origins prior to Cdt1 release and ORC-Cdc6-Mcm2-7 complex formation, but how the second Mcm2-7 hexamer is recruited to promote double-hexamer formation is not well understood. Here, structural evidence for intermediates consisting of an ORC-Cdc6-Mcm2-7 complex and an ORC-Cdc6-Mcm2-7-Mcm2-7 complex are reported, which together provide new insights into DNA licensing. Detailed structural analysis of the loaded Mcm2-7 double-hexamer complex demonstrates that the two hexamers are interlocked and misaligned along the DNA axis and lack ATP hydrolysis ...

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This graph shows the total number of publications written about Minichromosome Maintenance Complex Component 8 by people in this website by year, and whether Minichromosome Maintenance Complex Component 8 was a major or minor topic of these publications ...

TY - JOUR. T1 - Immunohistochemical expression of minichromosome maintenance complex protein 2 predicts biochemical recurrence in prostate cancer. T2 - A tissue microarray and digital imaging analysis-based study of 428 cases. AU - Toubaji, Antoun. AU - Sutcliffe, Siobhan. AU - Chaux, Alcides. AU - Lecksell, Kristen. AU - Hicks, Jessica. AU - De Marzo, Angelo M.. AU - Platz, Elizabeth A.. AU - Netto, George J.. PY - 2012/11/1. Y1 - 2012/11/1. N2 - Prostate cancer remains a major health problem in the United States. Established clinicopathologic parameters such as Gleason score, T stage, and prostate-specific antigen levels are currently the guiding tools for prognostication and disease management. The addition of biomarkers could increase the accuracy of these parameters for predicting disease progression, response to therapy, and survival. In this regard, the goal of this study was to evaluate minichromosome maintenance complex protein 2 and Ki-67 immunohistochemical expression as predictors of ...

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The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008 ...

Our data document spatial organisation of cell proliferation in normal oesophageal squamous epithelium and non-dysplastic Barretts mucosa, and disruption of this highly organised spatial arrangement in premalignant dysplasia. These disturbances are relevant to the identification of dysplasia in oesophageal squamous epithelium and Barretts mucosa, both of which are problematic in individuals and populations. Squamous oesophageal cancer is a target for screening in Far Eastern populations. Barretts oesophagus and Barretts cancer are relatively common in the West. Patients with Barretts oesophagus may be subjected to relatively frequent endoscopy and biopsy (for example, yearly). A sensitive and specific test for dysplasia might allow Barretts patients to be screened for dysplasia and divided into a cohort without dysplasia, at low risk of oesophageal adenocarcinoma, for whom less intensive follow up would be safe, and a higher risk group, with dysplasia, for whom more frequent endoscopic and ...

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MCM6 antibody (minichromosome maintenance complex component 6) for ICC/IF, IHC-P, WB. Anti-MCM6 pAb (GTX54353) is tested in Human, Mouse, Rat samples. 100% Ab-Assurance.

The outcomes of expressing the C788G allele of RBR3 suggest that the function(s) of RBR3 in cell cycle regulation and transformation requires an activity that is distinct from the canonical role of the pocket domain. The C788G mutation strongly diminishes the pocket binding activity of RBR3 (19). Ectopic expression of this allele would be expected to have no consequence if RBR3 function was exerted solely through its pocket domain, because an intact complement of RBR3 pocket activity would be retained due to the presence of endogenous RBR3. However, a marked reduction in MCM2-7 gene expression, DNA synthesis, and cell transformation was observed on expressing the C788G mutant allele. We interpret these outcomes as an indication of a requirement of RBR3 for an activity that is independent from its pocket domain. In the model shown in Fig. S4, we represent this unspecified activity as a protein or protein complex binding to the N-terminal region of RBR3. Overexpression of RBR3 with a functional ...

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported ...

Is predicted to contribute to 3-5 DNA helicase activity and single-stranded DNA helicase activity. Involved in chordate embryonic development; mitotic cell cycle; and negative regulation of apoptotic process. Predicted to localize to MCM complex and nucleus. Is expressed in several structures, including endoderm; head; nervous system; pronephric duct; and tail bud. Human ortholog(s) of this gene implicated in Meier-Gorlin syndrome 8. Orthologous to human MCM5 (minichromosome maintenance complex component 5 ...

Complete information for MCM6 gene (Protein Coding), Minichromosome Maintenance Complex Component 6, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

Emerging evidence suggests that CESC carries high risks of mortality and morbidity, which result from metastasis and recurrence, and the incidence to mortality ratio is nearly 50% [21]. Genetic factors play a key role in tumorigenesis and cancer progression [22]. However, the exact mechanism underlying CESC remains unknown. As of date, a number of oncogenes and cancer suppressor genes have been identified, some of which, including minichromosome maintenance complex component 2 (MCM2), DNA topoisomerase II alpha (TOP2A), and cyclin dependent kinase inhibitor 2A (CDKN2A), have been reported in CESC [23]. Nevertheless, novel classes of biomarkers with high specificity, sensitivity, and efficiency are required for the diagnosis and prognosis of CESC. In this study, we explored the gene expression profile and pathological mechanism of CESC using microarray-based bioinformatic analysis. We identified a new gene, NUSAP1, which is closely related to apoptosis, proliferation, and metastasis, and there is ...

Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex Shin-ichiro Hiraga, Gina M. Alvino, FuJung Chang, Hui-yong Lian, Akila Sridhar, Takashi Kubota, Bonita J. Brewer, Michael Weinreich, M.K. Raghuraman and Anne D. Donaldson Genes & Dev. 2014. 28: 372-383 ...

Mcm2, Mcm3, and Mcm5/Cdc46 are conserved proteins essential for the initiation of DNA synthesis at replication origins in Saccharomyces cerevisiae. The accumulation of these proteins in the nucleus before the onset of DNA synthesis suggests that they play a role in restricting DNA synthesis to once per cell cycle. In this work, we show that Mcm2, Mcm3, and Mcm5 self-interact and interact with one another to form complexes. Mcm2 and Mcm3 are abundant proteins, present in approximately 4 X 10(4) and 2 X 10(5) copies per cell, respectively. Reducing the dosage of Mcm2 by half results in diminished usage of specific replication origins. These results together suggest that a significant molar excess of Mcm proteins relative to replication origins is required for the proper initiation of all replication origins. ...

Background: Malignant melanoma is the most lethal form of skin cancer with a variable clinical course even in patients with thin melanomas and localized disease. Despite increasing insights into melanoma biology, no prognostic biomarkers have yet been incorporated into clinical protocols. Reduced expression of the RNA binding motif protein 3 (RBM3) has been shown to correlate with tumour progression and poor prognosis in melanoma and several other cancer forms. In ovarian cancer, an inverse association was found between expression of RBM3 and the minichromosome maintenance 3 (MCM3) gene and protein. In melanoma, gene expression analysis and immunohistochemical validation has uncovered MCM3 as a putative prognostic biomarker. The aim of the present study was to examine the associations of MCM3 expression with clinical outcome and RBM3 expression in a prospective, population-based cohort of melanoma.. Methods: Immunohistochemical MCM3 expression was examined in 224 incident cases of primary ...

The binary distribution of Mcm2‐7 across the genome prompted us to investigate genomic features that may be associated with the broad regions of high or low Mcm2‐7 levels along the chromosome. The Mcm2‐7 localization pattern relative to annotated genomic features suggested that Mcm2‐7 may be displaced by actively transcribed genes (Fig 5A). To quantitatively assess the Mcm2‐7 distribution relative to transcription units, we generated histograms of Mcm2‐7 enrichment for transcribed and non‐transcribed genes (Fig 5B) and found a bimodal pattern of Mcm2‐7 enrichment. Specifically, active genes had no or very little Mcm2‐7 signal, whereas inactive or non‐transcribed genes exhibited an elevated Mcm2‐7 signal (P , 1.02 × 10−257; t = 40.16). We also considered that the bimodal distribution of Mcm2‐7 enrichment between active and inactive genes might be due to the activation of early origins that are enriched near actively transcribed genes. However, we found that the bimodal ...

I bought 6 of these a few months back for ~\\\ each after MCMs discounts and was wondering if anybody else has tried playing with them. As is menti

The point I am trying to make is that while a dedicated MCM capability is required for dedicated mine hunting and clearance against all possible threats, a limited capability would be extremely useful for any platform that finds itself in the threat environment without an Avenger, MH-53E, or LCS with MCM mission package. Recent history has suggested a limited capability that would allow a ship to navigate itself out of a mine field could have prevented multiple ship losses. And that limited capability was proven in the recently conducted LCS MCM Mission Package TECHEVAL (completed in late FY15). There were certainly technical issues uncovered that I believe are being worked, but there is an opportunity to greatly expand deployment options with a limited but useful capability. The LCS mission package capabilities were intended to be a come as you are party, with capabilities developed under separate program of records and then integrated on the LCS. The airborne MCM capabilities for the LCS MCM ...

MCM3 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in the initiation of eukaryotic genome replication.…

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Samel, S. A., Fernández-Cid, A., Sun, J., Riera, A., Tognetti, S., Herrera, C., Li, H., Speck, C. (2014). A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2-7 onto DNA. Genes & Development 28, 1653-1666 ...