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DREAM Complex
The dimerization partner, RB-like, E2F and multi-vulval class B (DREAM) complex is a protein complex responsible for the regulation of cell cycle-dependent gene expression. The complex is evolutionarily conserved, although some of its components vary from species to species. In humans, the key proteins in the complex are RBL1 (p107) and RBL2 (p130), both of which are homologs of RB (p105) and bind repressive E2F transcription factors E2F4 and E2F5; DP1, DP2 and DP3, dimerization partners of E2F; and MuvB, which is a complex of LIN9/37/52/54 and RBBP4. Discovery Genes encoding the MuvB complex were originally identified from loss-of-function mutation studies in ''C. elegans''. When mutated, these genes produced worms with multiple vulva-like organs, hence the name ‘Muv’. Three classes of Muv genes were classified, with class B genes encoding homologues of mammalian RB, E2F, and DP1, and others such as LIN-54, LIN-37, LIN-7 and LIN-52, whose functions were not yet understo ...
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Cell Cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division. In cells with nuclei ( eukaryotes, i.e., animal, plant, fungal, and protist cells), the cell cycle is divided into two main stages: interphase and the mitotic (M) phase (including mitosis and cytokinesis). During interphase, the cell grows, accumulating nutrients needed for mitosis, and replicates its DNA and some of its organelles. During the mitotic phase, the replicated chromosomes, organelles, and cytoplasm separate into two new daughter cells. To ensure the proper replication of cellular components and division, there are control mechanisms known as cell cycle checkpoints after each of the key steps ...
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Mitosis
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is maintained. Therefore, mitosis is also known as equational division. In general, mitosis is preceded by S phase of interphase (during which DNA replication occurs) and is often followed by telophase and cytokinesis; which divides the cytoplasm, organelles and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis altogether define the mitotic (M) phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other. The process of mitosis is divided into stages corresponding to the completion of one set of activities and the start of the next. These stages are preprophase (specific to plant cells), prophase ...
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RNA Polymerase
In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that synthesizes RNA from a DNA template. Using the enzyme helicase, RNAP locally opens the double-stranded DNA so that one strand of the exposed nucleotides can be used as a template for the synthesis of RNA, a process called transcription. A transcription factor and its associated transcription mediator complex must be attached to a DNA binding site called a promoter region before RNAP can initiate the DNA unwinding at that position. RNAP not only initiates RNA transcription, it also guides the nucleotides into position, facilitates attachment and elongation, has intrinsic proofreading and replacement capabilities, and termination recognition capability. In eukaryotes, RNAP can build chains as long as 2.4 million nucleotides. RNAP produces RNA that, functionally, is either for protein coding, i.e. messenger RNA (mRNA); or n ...
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Nucleosome
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4. DNA must be compacted into nucleosomes to fit within the cell nucleus. In addition to nucleosome wrapping, eukaryotic chromatin is further compacted by being folded into a series of more complex structures, eventually forming a chromosome. Each human cell contains about 30 million nucleosomes. Nucleosomes are thought to carry epigenetically inherited information in the form of covalent modifications of their core histones. Nucleosome positions in the gen ...
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Chromatin Remodeling
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several ...
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Programmed Cell Death
Programmed cell death (PCD; sometimes referred to as cellular suicide) is the death of a cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usually confers advantage during an organism's lifecycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development. Apoptosis and autophagy are both forms of programmed cell death. Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Necrosis was long seen as a non-physiological process that occurs as a result of infection or injury, but in the 2000s, a form of programmed necrosis, called necroptosis, was recognized as an alternative form of programmed cell death. It is hypothesized that necroptosis ...
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Chromatin Immunoprecipitation
Chromatin immunoprecipitation (ChIP) is a type of immunoprecipitation experimental technique used to investigate the interaction between proteins and DNA in the cell. It aims to determine whether specific proteins are associated with specific genomic regions, such as transcription factors on promoters or other DNA binding sites, and possibly define cistromes. ChIP also aims to determine the specific location in the genome that various histone modifications are associated with, indicating the target of the histone modifiers. ChIP is crucial for the advancements in the field of epigenomics and learning more about epigenetic phenomena. Briefly, the conventional method is as follows: # DNA and associated proteins on chromatin in living cells or tissues are crosslinked (this step is omitted in Native ChIP). # The DNA-protein complexes (chromatin-protein) are then sheared into ~500 bp DNA fragments by sonication or nuclease digestion. # Cross-linked DNA fragments associated with the prot ...
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G0 And Early G1 DREAM Complex
G, or g, is the seventh letter in the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is ''gee'' (pronounced ), plural ''gees''. History The letter 'G' was introduced in the Old Latin period as a variant of ' C' to distinguish voiced from voiceless . The recorded originator of 'G' is freedman Spurius Carvilius Ruga, who added letter G to the teaching of the Roman alphabet during the 3rd century BC: he was the first Roman to open a fee-paying school, around 230 BCE. At this time, ' K' had fallen out of favor, and 'C', which had formerly represented both and before open vowels, had come to express in all environments. Ruga's positioning of 'G' shows that alphabetic order related to the letters' values as Greek numerals was a concern even in the 3rd century BC. According to some records, the original seventh letter, 'Z', had been purged from the Latin alphabet somewhat ear ...
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APC/C
Anaphase-promoting complex (also called the cyclosome or APC/C) is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C have unknown functions but are highly conserved. It was the discovery of the APC/C (and SCF) and their key role in eukaryotic cell-cycle regulation that established the importance of ubiquitin-mediated proteolysis in cell biology. Once perceived as a system exclusively involved in removing damaged protein from the cell, ubiquitination and subsequent protein degradation by the proteasome is now perceived as a universal regulatory mechanism for signal transduction whose importance approaches that of protein phosphorylation. In 2014, the APC/C was mapped in 3D at a resolution of less than a nanometre, which also uncovered its secondary structure. This finding could ...
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SCF Complex
Skp, Cullin, F-box containing complex (or SCF complex) is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal degradation. Along with the anaphase-promoting complex, SCF has important roles in the ubiquitination of proteins involved in the cell cycle. The SCF complex also marks various other cellular proteins for destruction. Core components SCF contains a variable F-box protein and three core subunits: *F-box protein (FBP) – FBP contributes to the substrate specificity of the SCF complex by first aggregating to target proteins independently of the complex. Each FBP (e.g. Skp2) may recognize several different substrates in a manner that is dependent on post-translational modifications such as phosphorylation or glycosylation. FBP then binds to Skp1 of the SCF complex using an F-box motif, bringing the target protein into proximity with the functional E2 ubiquitin-conjugating enzyme. FBP is also essential in reg ...
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AURKA
Aurora kinase A also known as serine/threonine-protein kinase 6 is an enzyme that in humans is encoded by the ''AURKA'' gene. Aurora A is a member of a family of mitotic serine/threonine kinases. It is implicated with important processes during mitosis and meiosis whose proper function is integral for healthy cell proliferation. Aurora A is activated by one or more phosphorylations and its activity peaks during the G2 phase to M phase transition in the cell cycle. Discovery The aurora kinases were first identified in 1990 during a cDNA screen of ''Xenopus'' eggs. The kinase discovered, Eg2, is now referred to as Aurora A. It was not until 1998, however, that Aurora A's meiotic and mitotic importance was realized. Aurora kinase family The human genome contains three members of the aurora kinase family: Aurora kinase A, Aurora kinase B and Aurora C kinase. The ''Xenopus'', ''Drosophila'', and ''Caenorhabditis elegans'' genomes, on the other hand, contain orthologues on ...
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