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Repressor

In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by binding to the operator or associated silencers. A DNA-binding repressor blocks the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes into messenger RNA. An RNA-binding repressor prevents translation of the mRNA into protein; this blocking of expression is called repression. If an inducer, a molecule that initiates the gene expression, is present it can interact with the repressor protein and detach it from the operator. RNA polymerase can transcribe the message. A corepressor is a molecule that can bind to repressor and make it bind to the operator which decreases transcription. A repressor that binds with a corepressor is termed an inactive repressor. One type of aporepressor is an important metabolic protein in bacteria; the above mechanism of repression is a type of a feedback mechanism because it only allows transcription to occur if a certain condition is present: the presence of specific inducer.

Within the eukaryotic genome are regions of DNA known as silencers. These DNA sequences bind to repressors to or repress the expression of a gene. Silencers can be located several bases downstream from the actual promoter of the gene. Repressors can have two binding sites: one for the silencer region and one for the promoter; this causes chromosome looping, allowing the promoter region and the silencer region to come to close proximity. LacZYA transcribes the proteins needed for lactose breakdown. LacI synthesizes the repressor of the lacZYA gene; the gene lacI is situated upstream of lacZYA but is transcribed from a different promoter. The lacI gene synthesizes LacI repressor protein; the LacI repressor protein represses lacZYA by binding to the operator sequence lacO. The lacZYA repressor is constitutively expressed, it is always bound to the operator region of the promoter, which interferes with the ability of RNA polymerase to begin transcription of the lacZYA operon. In the presence of the inducer allolactose, the repressor changes conformation and falls off the operator.

RNAP is able to bind to the promoter and begin transcription of the lacZYA gene. An example of a repressor protein is the methionine repressor MetJ. MetJ interacts with DNA bases via a ribbon-helix-helix motif. MetJ is a homodimer consisting of two monomers, which each provides a beta ribbon and an alpha helix. Together, the beta ribbons of each monomer come together to form an antiparallel beta-sheet which binds to the DNA operator in its major groove. Once bound, the MetJ dimer interacts with another MetJ dimer bound to the complementary strand of the operator via its alpha helices. AdoMet binds to a pocket in MetJ; the Met box has the sequence AGACGTCT, a palindrome allowing the same sequence to be recognised on either strand of the DNA. The junction between C and G in the middle of the Met box contains a pyrimidine-purine step that becomes positively supercoiled forming a kink in the phosphodiester backbone; this is how the protein checks for the recognition site as it allows the DNA duplex to follow the shape of the protein.

In other words, recognition happens through indirect readout of the structural parameters of the DNA, rather than via specific base sequence recognition. Each MetJ dimer contains two binding sites for the cofactor S-Adenosyl methionine, a product in the biosynthesis of methionine; when SAM is present, it binds to the MetJ protein, increasing its affinity for its cognate operator site, which halts transcription of genes involved in methionine synthesis. When SAM concentration becomes low, the repressor dissociates from the operator site, allowing more methionine to be produced. Promoter Activator Operon Regulation of gene expression Transcription factor lac repressor P300/CBP Glossary of gene expression terms Repressor+Proteins at the US National Library of Medicine Medical Subject Headings

Cicuta bulbifera

Cicuta bulbifera known as the bulb-bearing water-hemlock, is a plant native to North America and one of four species in the poisonous genus Cicuta. Tiny bulbils form in the leaf joints in the upper part of the plant, giving the plant its scientific and common names. Cicuta bulbifera can be distinguished from Cicuta douglasii by its narrow leaflet segments and its bulbil-bearing upper leaf axils; this native perennial plant reaches 1.5–3.5 feet tall with limited branching. The stems are light green to reddish and glaucous from epicuticular wax; the compound, alternate leaves are green glaucous, up to 1 by 0.5 feet, becoming smaller as they ascend the stems. Lower leaves are bipinnate, while the upper leaves are simple-pinnate; the petioles of the lower leaves are long, but those of the shorter leaves are much shorter or absent. Leaflets are up to 3 inches 0.33 inches across. The axils of the upper leaves have sessile clusters of ovoid bulbils, capable of giving rise to new plants; the root system consists of a cluster of elongated fleshy roots.

The stems terminate into compound umbels of small white flowers, each of which spans about 2–4 inches across and comprises about 8 umbellets, themselves each composed of some 16 flowers. The entire inflorescence is bractless. Flowers are about 1⁄8 inch across and consist of 5 white petals, 5 stamens, 2 styles, an ovary; the blooming period lasts about a month. There is no noticeable floral scent; each seed is contained in a fruit of the same size as the original flower, somewhat flattened, egg-shaped, notched at its apex. Cicuta bulbifera is native to North America and has a wide range of distribution from Newfoundland and Labrador to British Columbia in Canada, to Virginia, Indiana and Oregon in the United States. A perennial, it reproduces by its bulbils, it grows along the edges of marshes and lake margins, in bogs, wet meadows, shallow standing water and along slow-moving streams. It can grow on hummocks and floating mats, on submerged rotting logs, is known to grow on beaver dams; this species is found in high-quality wetlands.

All plant parts are poisonous to humans and livestock. The tuberous roots, stem base, young shoots are toxic. Livestock poisoning from Water Hemlocks is the most common in dry areas of the western United States, where grazing animals are drawn to low areas for green forage during dry spells; the poisonous properties of C. bulbifera are similar to those of other members of the genus Cicuta. The roots and rootstalks are the most poisonous parts of the plant, but all parts of the plant may contain some of the poison in the early stages of growth. Ingestion of a small portion of the root is enough to kill an adult; some would list these plants as the most poisonous occurring North American genus of leafy plants. Poisoning from these plants has been reported a number of times in human beings. Children and adults have consumed the roots mistaking them for parsnips or other roots with fatal results. Most cases of poisoning however occur in early spring; the quantity of C. bulbifera necessary to cause death varies with the age of the plant.

A piece of root about the size of a walnut is enough to cause the death of a cow. The symptoms of poisoning by C. bulbifera in human beings include pain in the stomach, violent vomiting, dilated pupils, labored breathing, foaming at the mouth and rapid convulsions. In animals the first symptom is frothing at the mouth followed by uneasiness and pain, succeeded by violent intermittent convulsions in which the animal kicks while throwing its head back; some suggested treatment is to give an efficient emetic, followed by a cathartic. If free vomiting is promptly produced, the patient is to recover. For cattle, injections of morphine have been recommended to treat convulsions and pain, but the convulsions are uncontrollable