5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole
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5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole
5,6-Dichloro-1-β--ribofuranosylbenzimidazole (DRB) is a chemical compound that inhibits transcription elongation by RNA Polymerase II. Sensitivity to DRB is dependent on DRB sensitivity inducing factor (DSIF), negative elongation factor (NELF), and positive transcription elongation factor b (P-TEFb). DRB is a nucleoside analog and also inhibits some 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 fu ...s. References Nucleosides Benzimidazoles Organochlorides Ribosides {{biochem-stub ...
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P-TEFb
The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II (Pol II) in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes (Figure 1). P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol IIMarshall NF, Peng J, Xie Z, Price DH. Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. J Biol Chem 1996; 271:27176-83. and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP.Peterlin BM, Brogie JE, Price DH. 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription. Wi ...
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DSIF
In gene expression, DSIF (DRB Sensitivity Inducing Factor) is a protein that can either negatively or positively affect transcription by RNA polymerase II (Pol II). In one case of negative regulation, it can interact with negative elongation factor (NELF) to promote the stalling of Pol II at some genes. This stalling is relieved by P-TEFb. In humans, DSIF is composed of hSPT4 and hSPT5 (SPT4 and SPT5 are homologs in yeast). The complex locks the RNAP clamp into a closed state to prevent the elongation complex (EC) from dissociating. The Spt5 NGN domain helps anneal the two strands of DNA upstream. The single KOW domain in bacteria and archaea anchors a ribosome Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ... to the RNAP. In bacteria, the homologous complex only contains ''Nus ...
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RNA Polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryotic cells. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to upstream gene promoters and begin transcription. Discovery Early studies suggested a minimum of two RNAPs: one which synthesized rRNA in the nucleolus, and one which synthesized other RNA in the nucleoplasm, part of the nucleus but outside the nucleolus. In 1969, science experimentalists Robert Roeder and William Rutter definitively discovered an additional RNAP that was responsible for transcription of some kind of RNA in the nucleoplasm. The finding was obtained by the use of ion-exchange chromatography via DEAE coated Sephadex beads. The technique separated the enzymes ...
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Negative Elongation Factor
In molecular biology, the NELF (negative elongation factor) is a four-subunit protein complex (NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E) that negatively impacts transcription by RNA polymerase II (Pol II) by pausing about 20-60 nucleotides downstream from the transcription start site (TSS). Structure The NELF has four subunits within its complex which are the following: NELF-A, NELF-B, NELF-C/NELF-D, and NELF-E. The NELF-A subunit is encoded by the gene WHSC2 (Wolf-Hirschhorn syndrome candidate 2). Micro-sequencing analysis demonstrated that NELF-B was the protein previously identified as being encoded by the gene COBRA1. It is unknown whether or not NELF-C and NELF-D are peptides resulting from the same mRNA with different translation initiation sites; possibly differing only in an extra 9 amino acids for NELF-C at the N-terminus, or peptides from different mRNAs entirely. A single NELF complex consists of either NELF-C or NELF-D, but not both. NELF-E is also known as RDBP. ...
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Nucleoside
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Nucleotides are the molecular building-blocks of DNA and RNA. List of nucleosides and corresponding nucleobases The reason for 2 symbols, shorter and longer, is that the shorter ones are better for contexts where explicit disambiguation is superfluous (because context disambiguates) and the longer ones are for contexts where explicit disambiguation is judged to be needed or wise. For example, when discussing long nucleobase sequences in genomes, the CATG symbol system is much preferable to the Cyt-Ade-Thy-Gua symbol system (see '' N ...
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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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Nucleosides
Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide is composed of a nucleobase, a five-carbon sugar, and one or more phosphate groups. In a nucleoside, the anomeric carbon is linked through a glycosidic bond to the N9 of a purine or the N1 of a pyrimidine. Nucleotides are the molecular building-blocks of DNA and RNA. List of nucleosides and corresponding nucleobases The reason for 2 symbols, shorter and longer, is that the shorter ones are better for contexts where explicit disambiguation is superfluous (because context disambiguates) and the longer ones are for contexts where explicit disambiguation is judged to be needed or wise. For example, when discussing long nucleobase sequences in genomes, the CATG symbol system is much preferable to the Cyt-Ade-Thy-Gua symbol system (see '' N ...
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Benzimidazoles
Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a colorless solid. Preparation Benzimidazole is produced by condensation of o-phenylenediamine with formic acid,. or the equivalent trimethyl orthoformate: :C6H4(NH2)2 + HC(OCH3)3 → C6H4N(NH)CH + 3 CH3OH 2-substituted derivatives are obtained when the condensation is conducted with aldehydes in place of formic acid, followed by oxidation.Robert A. Smiley "Phenylene- and Toluenediamines" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. Reactions Benzimidazole is a base: :C6H4N(NH)CH + H+ → 6H4(NH)2CHsup>+ It can also be deprotonated with stronger bases: :C6H4N(NH)CH + LiH → Li 6H4N2CH + H2 The imine can be alkylated and also serves as a ligand in coordination chemistry. The most prominent benzimidazole complex features ''N''-ribosyl-dimethylbenzimidazole as foun ...
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Organochlorides
An organochloride, organochlorine compound, chlorocarbon, or chlorinated hydrocarbon is an organic compound containing at least one covalently bonded atom of chlorine. The chloroalkane class (alkanes with one or more hydrogens substituted by chlorine) provides common examples. The wide structural variety and divergent chemical properties of organochlorides lead to a broad range of names, applications, and properties. Organochlorine compounds have wide use in many applications, though some are of profound environmental concern, with TCDD being one of the most notorious. Physical and chemical properties Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage. Natural occurrence Many organochlorine compounds have been isolate ...
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