Origin Recognition Complex
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Origin Recognition Complex
In molecular biology, origin recognition complex (ORC) is a multi-subunit DNA binding complex (6 subunits) that binds in all eukaryotes and archaea in an ATP-dependent manner to origins of replication. The subunits of this complex are encoded by the ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6 genes. ORC is a central component for eukaryotic DNA replication, and remains bound to chromatin at replication origins throughout the cell cycle. ORC directs DNA replication throughout the genome and is required for its initiation. ORC and Noc3p bound at replication origins serve as the foundation for assembly of the pre-replication complex (pre-RC), which includes Cdc6, Tah11 (a.k.a. Cdt1), and the Mcm2-Mcm7 complex. Pre-RC assembly during G1 is required for replication licensing of chromosomes prior to DNA synthesis during S phase. Cell cycle-regulated phosphorylation of Orc2, Orc6, Cdc6, and MCM by the cyclin-dependent protein kinase Cdc28 regulates initiation of DNA replication, including ...
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Molecular Biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physical structure of biological macromolecules is known as molecular biology. Molecular biology was first described as an approach focused on the underpinnings of biological phenomena - uncovering the structures of biological molecules as well as their interactions, and how these interactions explain observations of classical biology. In 1945 the term molecular biology was used by physicist William Astbury. In 1953 Francis Crick, James Watson, Rosalind Franklin, and colleagues, working at Medical Research Council unit, Cavendish laboratory, Cambridge (now the MRC Laboratory of Molecular Biology), made a double helix model of DNA which changed the entire research scenario. They proposed the DNA structure based on previous research done by Ro ...
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Pre-replication Complex
A pre-replication complex (pre-RC) is a protein complex that forms at the origin of replication during the initiation step of DNA replication. Formation of the pre-RC is required for DNA replication to occur. Complete and faithful replication of the genome ensures that each daughter cell will carry the same genetic information as the parent cell. Accordingly, formation of the pre-RC is a very important part of the cell cycle. Components As organisms evolved and became increasingly more complex, so did their pre-RCs. The following is a summary of the components of the pre-RC amongst the different domains of life. In bacteria, the main component of the pre-RC is DnaA. The pre-RC is complete when DnaA occupies all of its binding sites within the bacterial origin of replication (oriC). The archaeal pre-RC is very different from the bacterial pre-RC and can serve as a simplified model of the eukaryotic pre-RC. It is composed of a single origin recognition complex (ORC) protein, Cd ...
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G2 Phase
G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the onset of prophase, the first phase of mitosis in which the cell’s chromatin condenses into chromosomes. G2 phase is a period of rapid cell growth and protein synthesis during which the cell prepares itself for mitosis. Curiously, G2 phase is not a necessary part of the cell cycle, as some cell types (particularly young ''Xenopus'' embryos and some cancers)) proceed directly from DNA replication to mitosis. Though much is known about the genetic network which regulates G2 phase and subsequent entry into mitosis, there is still much to be discovered concerning its significance and regulation, particularly in regards to cancer. One hypothesis is that the growth in G2 phase is regulated as a method of cell size control. Fission yeast (''Schi ...
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Cdc28
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast ''S. cerevisiae'', and the fission yeast ''S. pombe'', where it is encoded by genes ''cdc28'' an''cdc2'' respectively. With its cyclin partners, Cdk1 forms complexes that phosphorylate a variety of target substrates (over 75 have been identified in budding yeast); phosphorylation of these proteins leads to cell cycle progression. Structure Cdk1 is a small protein (approximately 34 kilodaltons), and is highly conserved. The human homolog of Cdk1, ''CDK1'', shares approximately 63% amino-acid identity with its yeast homolog. Furthermore, human ''CDK1'' is capable of rescuing fission yeast carrying a ''cdc2'' mutation. Cdk1 is comprised mostly by the bare protein kinase motif, which other protein kinases share. Cdk1, li ...
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Protein Kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein ( substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets and most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction. Chemical ac ...
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Cyclin
Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle. Etymology Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urchins. In an interview for "The Life Scientific" (aired on 13/12/2011) hosted by Jim Al-Khalili, R. Timothy Hunt explained that the name "cyclin" was originally named after his hobby cycling. It was only after the naming did its importance in the cell cycle become apparent. As it was appropriate the name stuck. R. Timothy Hunt: "By the way, the name cyclin, which I coined, was really a joke, it's because I liked cycling so much at the time, but they did come and go in the cell..." Function Cyclins were originally named because their concentration varies in a cyclical fashion during the cell cycle. (Note that the cyclins are now classified according to their conse ...
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Phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many enzymes. Glucose Phosphorylation of sugars is often the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by :D-glucose + ATP → D-glucose-6-phosphate + ADP : ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition) Hepatic cells are freely permeable to glucose, and ...
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S Phase
S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved. Regulation Entry into S-phase is controlled by the G1 restriction point (R), which commits cells to the remainder of the cell-cycle if there is adequate nutrients and growth signaling. This transition is essentially irreversible; after passing the restriction point, the cell will progress through S-phase even if environmental conditions become unfavorable. Accordingly, entry into S-phase is controlled by molecular pathways that facilitate a rapid, unidirectional shift in cell state. In yeast, for instance, cell growth induces accumulation of Cln3 cyclin, which complexes with the cyclin dependent kinase CDK2. The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating ...
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Chromosomes
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are the histones. These proteins, aided by chaperone proteins, bind to and condense the DNA molecule to maintain its integrity. These chromosomes display a complex three-dimensional structure, which plays a significant role in transcriptional regulation. Chromosomes are normally visible under a light microscope only during the metaphase of cell division (where all chromosomes are aligned in the center of the cell in their condensed form). Before this happens, each chromosome is duplicated (S phase), and both copies are joined by a centromere, resulting either in an X-shaped structure (pictured above), if the centromere is located equatorially, or a two-arm structure, if the centromere is located distally. The joined copies are now called sis ...
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Licensing Factor
A licensing factor is a protein or complex of proteins that allows an origin of replication to begin DNA replication at that site. Licensing factors primarily occur in eukaryotic cells, since bacteria use simpler systems to initiate replication. However, many archaea use homologues of eukaryotic licensing factors to initiate replication. Function Origins of replication represent start sites for DNA replication and so their "firing" must be regulated to maintain the correct karyotype of the cell in question. The origins are required to fire only once per cell cycle, an observation that led to the postulated existence of licensing factors by biologists in the first place. If the origins were not carefully regulated then DNA replication could be restarted at that origin giving rise to multiple copies of a section of DNA. This could be damaging to cells and could have detrimental effects on the organism as a whole. The control that licensing factors exert over the cycle represents a f ...
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G1 Phase
The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. G1 phase ends when the cell moves into the S phase of interphase. Around 30 to 40 percent of cell cycle time is spent in the G1 phase. Overview G1 phase together with the S phase and G2 phase comprise the long growth period of the cell cycle cell division called interphase that takes place before cell division in mitosis (M phase). During G1 phase, the cell grows in size and synthesizes mRNA and protein that are required for DNA synthesis. Once the required proteins and growth are complete, the cell enters the next phase of the cell cycle, S phase. The duration of each phase, including the G1 phase, is different in many different types of cells. In human somatic cells, the cell cycle lasts about 10 hours, and the G1 H ...
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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 p ...
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