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MCM6
DNA replication licensing factor MCM6 is a protein that in humans is encoded by the ''MCM6'' gene. MCM6 is one of the highly conserved mini-chromosome maintenance proteins ( MCM) that are essential for the initiation of eukaryotic genome replication. Function The MCM complex consisting of MCM6 (this protein) and MCM2, 4 and 7 possesses DNA helicase activity, and may act as a DNA unwinding enzyme. 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 phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication. Mcm 6 has recently been shown to interact strongly Cdt1 at defined residues, by mutating these target residues Wei ''et al''. observed lack of Cdt1 recruitment of Mcm2-7 to the pre-RC. Gene The MCM6 gene, ' ...
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Mini Chromosome Maintenance
The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer. As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest checkpoints. Both the loading and activation of MCM helicase are strictly regulated and are coupled to cell growth cycles. Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas. History and structure The minichromosome maintenance proteins were named after a yeast genetics screen for mutants defective in the regulation of DNA replication initiation. The rationale behind this screen was that if replication origins were regulated in a manner analogous to transcription promoters, where transcriptional regulators showed promoter specificity, then replication regulators should also show origin specificity. Since ...
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MCM7
DNA replication licensing factor MCM7 is a protein that in humans is encoded by the ''MCM7'' gene. Function 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 tumor suppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported. Interactions MCM7 has been shown to interact with: * CDC45-related pr ...
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Cdt1
CDT1 (Chromatin licensing and DNA replication factor 1) is a protein that in humans is encoded by the ''CDT1'' gene. It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle. Role in pre-replication complexes The protein encoded by this gene is a key licensing factor in the assembly of pre-replication complexes (pre-RC), which occurs during the G1 phase of the cell cycle. In the assembly of pre-RCs, origin recognition complexes (ORC1-6) recognize and bind to DNA replication origins. CDT1, along with the protein CDC6, are then recruited to the forming pre-RC, followed by minichromosome maintenance complexes (MCM2-7). The activity of CDT1 during the cell cycle is tightly regulated during the S phase by the protein geminin, which inhibits it, and by SCFSKP2, which ubiquinates the protein to tag it for proteasomal degradation. This regulation is important in preventing relicensing, thus ensuring that DNA is only replicated once per cell cy ...
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Lactose Tolerance
Lactase persistence is the continued activity of the lactase enzyme in adulthood, allowing the digestion of lactose in milk. In most mammals, the activity of the enzyme is dramatically reduced after weaning. In some human populations, though, lactase persistence has recently evolved as an adaptation to the consumption of nonhuman milk and dairy products beyond infancy. Lactase persistence is very high among northern Europeans, especially Irish people. Worldwide, most people are lactase ''non''-persistent, and are affected by varying degrees of lactose intolerance as adults. However, lactase persistence and lactose intolerance do not always overlap. Global distribution of the phenotype The distribution of the lactase persistence (LP) phenotype, or the ability to digest lactose into adulthood, is not homogeneous in the world. Lactase persistence frequencies are highly variable. In Europe, the distribution of the lactase persistence phenotype is clinal, with frequencies ranging from ...
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CDC45-related Protein
CDC45 is a protein that in humans is encoded by the ''CDC45L'' gene. Function The protein encoded by this gene was identified by its strong similarity with Saccharomyces cerevisiae Cdc45, an essential protein required to the initiation of DNA replication. Cdc45 is a member of the highly conserved multiprotein complex including Cdc6/Cdc18, the minichromosome maintenance proteins (MCMs) and DNA polymerase, which is important for early steps of DNA replication in eukaryotes. This protein has been shown to interact with MCM7 and DNA polymerase alpha. Studies of the similar gene in Xenopus suggested that this protein plays a pivotal role in the loading of DNA polymerase alpha onto chromatin. Multiple polyadenlyation sites of this gene are reported. Interactions CDC45-related protein has been shown to interact with: * MCM3, * MCM6, * MCM7 DNA replication licensing factor MCM7 is a protein that in humans is encoded by the ''MCM7'' gene. Function The protein encoded by this ge ...
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Lactase
Lactase is an enzyme produced by many organisms. It is located in the brush border of the small intestine of humans and other mammals. Lactase is essential to the complete digestion of whole milk; it breaks down lactose, a sugar which gives milk its sweetness. People who have deficiency of lactase, and consume dairy products, may experience the symptoms of lactose intolerance. Lactase can be purchased as a food supplement, and is added to milk to produce "lactose-free" milk products. Lactase (also known as lactase-phlorizin hydrolase, or LPH), a part of the β-galactosidase family of enzymes, is a glycoside hydrolase involved in the hydrolysis of the disaccharide lactose into constituent galactose and glucose monomers. Lactase is present predominantly along the brush border membrane of the differentiated enterocytes lining the villi of the small intestine. In humans, lactase is encoded by the LCT gene on chromosome 2. Uses Food use Lactase is an enzyme that some peo ...
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ORC1L
Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene. It is closely related to CDC6, and both are the same protein in archaea. Function The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of the pre-replication complex, which includes additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is the largest subunit of the origin recognition complex. While other ORC subunits are stable throughout the cell cycle, the levels of this protein vary during the cell cycle, which has been shown to be controlled by ubiquitin-mediated proteolysis after initiation of DNA replication. This protein is found to be selectively phosphorylated during mitosis. It is also reported to intera ...
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MCM4
DNA replication licensing factor MCM4 is a protein that in humans is encoded by the ''MCM4'' gene. Function 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 trans ...
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MCM2
DNA replication licensing factor MCM2 is a protein that in humans is encoded by the ''MCM2'' gene. Function The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in 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. This protein forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7. Interactions MCM2 has been shown to interact with: * AKAP8, * Cell division cycle 7-related protein kinase, * MCM3, * MCM4, * MCM5, * MCM6, * MCM7, * ORC1L, * ORC2L, * ORC4L, * ORC5L, and * Replication protein A1. See also *Mini Chromosome Mai ...
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ORC2L
Origin recognition complex subunit 2 is a protein that is encoded by the ORC2 (ORC2L) gene in humans. Function The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is a subunit of the ORC complex. This protein forms a core complex with ORC3, ORC4, and ORC5. It also interacts with CDC45L and MCM10, which are proteins known to be important for the initiation of DNA replication. This protein has been demonstrated to specifically associate with the origin of replication of Epstein-Barr virus in human cells, and is thought to be required for DNA replication from viral origin of replication. Interactions ORC2 has been shown to interact with: * CDC6, * ...
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ORC4L
Origin recognition complex subunit 4 is a protein that in humans is encoded by the ORC4 (ORC4L) gene. Function The origin recognition complex (ORC) is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is a subunit of the ORC complex. It has been shown to form a core complex with ORC2L, -3L, and -5L. Three alternatively spliced transcript variants encoding the same protein have been reported. Interactions ORC4 has been shown to interact with: * MCM2, * MCM3, * MCM4, * MCM6, * ORC1, * ORC2, * ORC3, * ORC5, and * ORC6 Origin recognition complex subunit 6 is a protein that in humans is encoded by the ORC6 (ORC6L) gene. Background The origin recognition complex (ORC) is a highly ...
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Replication Protein A1
Replication protein A 70 kDa DNA-binding subunit is a protein that in humans is encoded by the ''RPA1'' gene. Interactions Replication protein A1 has been shown to interact with: * BRCA2, * BLM, * MCM2, * MCM4, * MCM6, * MCM7, * MUTYH, * ORC2L, * ORC6L, * P53, * RPA2, * RPA3, * TIPIN, * TP53BP1, and * XPA. See also * Replication protein A * Replication protein A2 * Replication protein A3 * Single-stranded binding protein Single-stranded binding proteins (SSBs) are a class of proteins that have been identified in both viruses and organisms from bacteria to humans. Viral SSB Although the overall picture of ''human cytomegalovirus'' (HHV-5) DNA synthesis appears ... References Further reading

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