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 Recognition Complex (ORC), Cdc6, and Cdt1. ORC, Cdc6, and MCM are members of the AAA+ family of ATPase...

To initiate DNA replication, cells first load an MCM helicase double hexamer at origins in a reaction requiring ORC, Cdc6, and Cdt1, also called pre-replicative complex (pre-RC) assembly. The essential mechanistic role of Cdc6 ATP hydrolysis in this reaction is still incompletely understood. Here, we show that although Cdc6 ATP hydrolysis is essential to initiate DNA replication, it is not esse...

Genetic studies, together with amino acid and structural similarities to the clamp loaders of DNA polymerase sliding clamps, have suggested that the Cdc6 protein may function as a loader for the eukaryotic replicative helicase, the minichromosome maintenance (MCM) complex. Thus, Cdc6 may act as the functional homologue of the bacterial DnaC that utilizes ATP hydrolysis to assemble the DnaB heli...

Multi-compartment diffusion models (MCM) are increasingly used to characterize the brain white matter microstructure from diffusion MRI. We address the problem of interpolation and averaging of MCM images as a simplification problem based on spectral clustering. As a core part of the framework, we propose novel solutions for the averaging of MCM compartments. Evaluation is performed both on syn...

We present a Meta–Cognitive Model (MCM) of attitudes. According to the MCM, an attitude object can be associated with both positive and negative evaluations that can be detected with modern implicit (automatic) measures of attitudes. These evaluative associations can be further associated with validity tags that are also consulted when completing deliberative attitude measures. We explain how t...

Background: Dendritic cells (DC) induce tumor or pathogen-specific T cell responses in humans. Several laboratories have developed culture systems, including maturation factors for human DC from peripheral blood monocytes. We comprehensively compared standard maturation stimulus, an autologous monocyte-conditioned medium (MCM), with heparin for their ability to promote uniformly mature DC that ...

The eukaryotic pre-replication complex is assembled at replication origins in a reaction called licensing. Licensing involves the interactions of a variety of proteins including the origin recognition complex (ORC), Cdc6 and the Mcm2-7 helicase, homologues of which are also found in archaea. The euryarchaeote Archaeoglobus fulgidus encodes two genes with homology to Orc/Cdc6 and a single Mcm ho...

The minichromosome maintenance (MCM) gene family is essential for DNA replication and is frequently upregulated in various cancers. Here, we examined the role of MCM2 in prostate cancer and the effect of microRNA-1296 (miR-1296), genistein, and trichostatin A (TSA) on the MCM complex. Profiling results showed that expression of MCM genes was higher in tumor samples. Genistein and TSA significan...

Multi-Chip Modules (MCM's) provide a medium for integration of several bare dies on a multi-layer substrate. MCM technology has gained popularity in recent years with the promise of orders of magnitude reduction in inter-chip delay and power dissipation over single chip packaging [2]. By virtue of a faster interconnect MCM's aim at alleviating, to a large extent, the bottleneck o ered by conven...

In this study, we investigated the basis of the resistance of muscles to tumor metastases. We found that a low molecular weight fraction (Mr <3000) of skeletal muscle cell-conditioned medium (MCM) markedly inhibits the proliferation of carcinoma, sarcoma, or melanoma cell lines in vitro. The MCM exerts a cytostatic effect on tumor cell growth and arrests the cells in G0/G1 of the cell cycle. Ho...