Replicating large eukaryotic genomes presents the challenge of distinguishing replicated regions of DNA from unreplicated DNA. A heterohexamer of minichromosome maintenance (MCM) proteins is essential for the initiation of DNA replication. MCM proteins are loaded on to unreplicated DNA before replication begins and displaced progressively during replication. Thus, bound MCM proteins license DNA...

Minichromosome maintenance (MCM) proteins play an essential role in DNA unwinding and are completely conserved throughout eukaryotic and archaeal cells, underscoring their fundamental importance in DNA replication. Biochemists have characterized some of the protein motifs that affect the unwinding of DNA by MCM proteins. Elizabeth Jenkinson and James Chong studied how changes in the MCM protein...

In animals, cobalamin (Cbl) is a cofactor for methionine synthase and methylmalonyl-CoA mutase (MCM), which utilizes methylcobalamin and 5'-deoxyadenosylcobalamin (AdoCbl), respectively. The cblA complementation class of inborn errors of Cbl metabolism in humans is one of three known disorders that affect AdoCbl synthesis. The gene responsible for cblA has been identified in humans (MMAA) as we...

The minichromosome maintenance complex (MCM) represents the replicative DNA helicase both in eukaryotes and archaea. Here, we describe the solution structure of the C-terminal domains of the archaeal MCMs of Sulfolobus solfataricus (Sso) and Methanothermobacter thermautotrophicus (Mth). Those domains consist of a structurally conserved truncated winged helix (WH) domain lacking the two typical ...

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is very difficult to treat with conventional chemotherapeutic regimens. Gemcitabine and 5-fluorouracil are used in the management of PDAC and act by indirectly blocking replicative forks. However, these drugs are not highly effective at suppressing disease progression, indicating a need for the development of in...

Cre-loxP technology for conditional gene inactivation is a powerful tool in cardiovascular research. Induction of gene inactivation can be carried out by per oral or intraperitoneal tamoxifen administration. Unintended transient cardiomyopathy following tamoxifen administration for gene inactivation has recently been reported. We aimed to develop a protocol for tamoxifen-induced gene inactivati...

BACKGROUND AND OBJECTIVES There is ongoing growth of elderly populations with ESRD in Western Europe and North America. In our center, we offer an alternative care pathway of 'maximum conservative management' (MCM) to patients who elect not to start dialysis, often because of a heavy burden of comorbid illness and advanced age. The objective of our study was to compare clinical outcomes for pat...

Introduction BioSense is a national human health surveillance system for disease detection, monitoring, and situation awareness through near realtime access to existing electronic healthcare encounter information, including information from hospital emergency departments (EDs). MCM include antibiotics, antivirals, antidotes, antitoxins, vaccinations, nuclide-binding agents, and other medication...

In S. cerevisiae, the chromatin structure of DNA replication origins changes as cells become competent for DNA replication, suggesting that G1 phase-specific association of replication factors with origin DNA regulates entry into S phase. We demonstrate that ORC, Cdc45p, and MCM proteins are components of prereplication complexes (pre-RC). The MCM-origin association is dependent upon ORC and Cd...