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DNA Glycosylase
DNA glycosylases are a family of enzymes involved in base excision repair, classified under EC number EC 3.2.2. Base excision repair is the mechanism by which damaged bases in DNA are removed and replaced. DNA glycosylases catalyze the first step of this process. They remove the damaged nitrogenous base while leaving the sugar-phosphate backbone intact, creating an apurinic/apyrimidinic site, commonly referred to as an AP site. This is accomplished by flipping the damaged base out of the double helix followed by cleavage of the N-glycosidic bond. Glycosylases were first discovered in bacteria, and have since been found in all kingdoms of life. In addition to their role in base excision repair, DNA glycosylase enzymes have been implicated in the repression of gene silencing in ''A. thaliana'', ''N. tabacum'' and other plants by active demethylation. 5-methylcytosine residues are excised and replaced with unmethylated cytosines allowing access to the chromatin structure of the ...
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Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the react ...
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SMUG1
Single-strand selective monofunctional uracil DNA glycosylase is an enzyme that in humans is encoded by the ''SMUG1'' gene. SMUG1 is a glycosylase that removes uracil from single- and double-stranded DNA in nuclear chromatin, thus contributing to base excision repair. Function SMUG1 is an important Uracil-DNA glycosylase, uracil-DNA glycosylases that process uracil in DNA. SMUG1 function is to remove U or its derivatives from DNA. SMUG1 is able to excise uracil from both single- and doubledstranded DNA. Other DNA glycosylases linked to U removal are Uracil-DNA glycosylase, UNG, Thymine-DNA glycosylase, TDG and MBD4. Uracil-DNA repair is essential to protect against mutations. Current evidence suggests that UNG and SMUG1 are the major enzymes responsible for the repair of the U:G mispairs. Uracil is also introduced into DNA as part of antibody gene diversification and its removal is critical to antibody diversification. UNG is known to be the major player in uracil removal but wh ...
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DNA Replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritance. This is essential for cell division during growth and repair of damaged tissues, while it also ensures that each of the new cells receives its own copy of the DNA. The cell possesses the distinctive property of division, which makes replication of DNA essential. DNA is made up of a double helix of two complementary strands. The double helix describes the appearance of a double-stranded DNA which is thus composed of two linear strands that run opposite to each other and twist together to form. During replication, these strands are separated. Each strand of the original DNA molecule then serves as a template for the production of its counterpart, a process referred to as semiconservative replication. As a result of semi-conservative re ...
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Thermophilic
A thermophile is an organism—a type of extremophile—that thrives at relatively high temperatures, between . Many thermophiles are archaea, though they can be bacteria or fungi. Thermophilic eubacteria are suggested to have been among the earliest bacteria. Thermophiles are found in various geothermally heated regions of the Earth, such as hot springs like those in Yellowstone National Park (see image) and deep sea hydrothermal vents, as well as decaying plant matter, such as peat bogs and compost. Thermophiles can survive at high temperatures, whereas other bacteria or archaea would be damaged and sometimes killed if exposed to the same temperatures. The enzymes in thermophiles function at high temperatures. Some of these enzymes are used in molecular biology, for example the ''Taq'' polymerase used in PCR. "Thermophile" is derived from the el, θερμότητα (''thermotita''), meaning heat, and el, φίλια (''philia''), love. Classification Thermophiles can be c ...
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Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of ...
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DNA Repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). This can eventually lead to malign ...
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Uracil
Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine (T). Uracil is a demethylated form of thymine. Uracil is a common and naturally occurring pyrimidine derivative. The name "uracil" was coined in 1885 by the German chemist Robert Behrend, who was attempting to synthesize derivatives of uric acid. Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein; it was also found in bovine thymus and spleen, herring sperm, and wheat germ. It is a planar, unsaturated compound that has the ability to absorb light. Based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, it is believed that uracil, xanthine, and related molecules can also be formed extraterrestrially. Data from the Cassini mission, orbiting in th ...
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Cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an amine group at position 4 and a keto group at position 2). The nucleoside of cytosine is cytidine. In Watson-Crick base pairing, it forms three hydrogen bonds with guanine. History Cytosine was discovered and named by Albrecht Kossel and Albert Neumann in 1894 when it was hydrolyzed from calf thymus tissues. A structure was proposed in 1903, and was synthesized (and thus confirmed) in the laboratory in the same year. In 1998, cytosine was used in an early demonstration of quantum information processing when Oxford University researchers implemented the Deutsch-Jozsa algorithm on a two qubit nuclear magnetic resonance quantum computer (NMRQC). In March 2015, NASA scientists reported the formation of cytosine, along with uracil and ...
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Deamination
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of excess protein intake, deamination is used to break down amino acids for energy. The amino group is removed from the amino acid and converted to ammonia. The rest of the amino acid is made up of mostly carbon and hydrogen, and is recycled or oxidized for energy. Ammonia is toxic to the human system, and enzymes convert it to urea or uric acid by addition of carbon dioxide molecules (which is not considered a deamination process) in the urea cycle, which also takes place in the liver. Urea and uric acid can safely diffuse into the blood and then be excreted in urine. Deamination reactions in DNA Cytosine Spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process. This can occur in vitro th ...
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Mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA (such as pyrimidine dimers caused by exposure to ultraviolet radiation), which then may undergo error-prone repair (especially microhomology-mediated end joining), cause an error during other forms of repair, or cause an error during replication ( translesion synthesis). Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements. Mutations may or may not produce detectable changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes including: evolution, cancer, and the development of the immune system, including junctional diversity. Mutation is the ultimate so ...
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Uracil-DNA Glycosylase
Uracil-DNA glycosylase is also known as UNG or UDG. Its most important function is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosidic bond and initiating the base-excision repair (BER) pathway. Function The human gene encodes one of several uracil-DNA glycosylases. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosidic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. After a mutation occurs, the mutagenic threat of uracil propagates through any subsequent DNA replication steps. Once unzipped, mismatched guanine and uracil pairs are separated, and DNA polymerase inserts complementary bases to form a guanine-cytosine (GC) pair in ...
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