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Activation-induced Cytidine Deaminase
Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the ''AICDA'' gene. It creates mutations in DNA by deamination of cytosine base, which turns it into uracil (which is recognized as a thymine). In other words, it changes a C:G base pair into a U:G mismatch. The cell's DNA replication machinery recognizes the U as a T, and hence C:G is converted to a T:A base pair. During germinal center development of B lymphocytes, error-prone DNA repair following AID action also generates other types of mutations, such as C:G to A:T. AID is a member of the APOBEC family. In B cells in the lymph nodes, AID causes mutations that produce antibody diversity, but that same mutation process can also lead to B cell lymphoma. Function This gene encodes a DNA-editing deaminase that is a member of the cytidine deaminase family. The protein is involved in somatic hypermutation, gene conver ...
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Kilodalton
The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted for use with SI. The word "unified" emphasizes that the definition was accepted by both IUPAP and IUPAC. The atomic mass constant, denoted , is defined identically. Expressed in terms of , the atomic mass of carbon-12: . Its value in SI units is an experimentally determined quantity. The 2022 CODATA recommended value of the atomic mass constant expressed in the SI base unit kilogram is:This value serves as a conversion factor of mass from daltons to kilograms, which can easily be converted to grams and other metric units of mass. The 2019 revision of the SI redefined the kilogram by fixing the value of the Planck constant (), improving the precision of the atomic mass constant expressed in SI units by anchoring it to fixed physical ...
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Gene Conversion
Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another allele, or ectopic, meaning that one Sequence homology#Paralogy, paralogous DNA sequence converts another. Allelic gene conversion Allelic gene conversion occurs during meiosis when homologous recombination between heterozygotic sites results in a mismatch in base pairing. This mismatch is then recognized and corrected by the cellular machinery causing one of the alleles to be converted to the other. This can cause non-Mendelian segregation of alleles in germ cells. Nonallelic/ectopic gene conversion Recombination occurs not only during meiosis, but also as a mechanism for repair of double-strand breaks (DSBs) caused by DNA damage. These DSBs are usually repaired using the sister chromatid of the broken duplex and not the homologous chrom ...
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DNA Polymerase Eta
DNA polymerase eta (Pol η), is a protein that in humans is encoded by the ''POLH'' gene. DNA polymerase eta is a eukaryotic DNA polymerase involved in the DNA repair by translesion synthesis. The gene encoding DNA polymerase eta is POLH, also known as XPV, because loss of this gene results in the disease xeroderma pigmentosum. Polymerase eta is particularly important for allowing accurate translesion synthesis of DNA damage resulting from ultraviolet radiation or UV. Function This gene encodes a member of the Y family of specialized DNA polymerases. It copies undamaged DNA with a lower fidelity than other DNA-directed polymerases. However, it accurately replicates UV-damaged DNA; when thymine dimers are present, this polymerase inserts the complementary nucleotides in the newly synthesized DNA, thereby bypassing the lesion and suppressing the mutagenic effect of UV-induced DNA damage. This polymerase is thought to be involved in hypermutation during immunoglobulin class ...
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Translesion Synthesis
DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified in Cell (biology), cells, by internal metabolism, metabolic by-products, and by external ionizing radiation, ultraviolet light, and medicines, resulting in spontaneous DNA damage involving tens of thousands of individual molecular lesions per cell per day. DNA modifications can also be programmed. Molecular lesions can cause structural damage to the DNA molecule, and can alter or eliminate the cell's ability for Transcription (biology), transcription and gene expression. Other lesions may induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells following mitosis. Consequently, DNA repair as part of the DNA damage response (DDR) is constantly active. When normal repair proce ...
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Pyrimidine
Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine (nitrogen atoms at the 1 and 4 positions) and pyridazine (nitrogen atoms at the 1 and 2 positions). In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine (C), thymine (T), and uracil (U). Occurrence and history The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. It is also found in many synthetic compounds such as barbiturates and the HIV drug zidovudine. Although pyrimidine derivatives such as alloxan were known in the early 19th century, a laboratory synthesis of a pyrimidine was not carried out until 1879, when Grimaux repor ...
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Purine
Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines and their tautomers. They are the most widely occurring nitrogen-containing heterocycles in nature. Dietary sources Purines are found in high concentration in meat and meat products, especially internal organs, such as liver and kidney, and in various seafoods, high-fructose beverages, alcohol, and yeast products. Examples of high-purine food sources include anchovies, sardines, liver, beef, kidneys, brains, monkfish, dried mackerel, and shrimp. Foods particularly rich in hypoxanthine, adenine, and guanine lead to higher blood levels of uric acid. Foods having more than 200 mg of hypoxanthine per 100 g, particularly animal and fish meats containing hypoxanthine as more than 50% of total purines, are more likely to increase uri ...
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Uracil-DNA Glycosylase
Uracil-DNA glycosylase (also known as UNG or UDG) is an enzyme. 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 ...
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5-methylcytosine
5-Methylcytosine (5mC) is a methylation, methylated form of the DNA base cytosine (C) that regulates gene Transcription (genetics), transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the Gene expression#DNA methylation and demethylation in transcriptional regulation, expression of methylated genes can be altered (the study of this is part of the field of epigenetics). 5-Methylcytosine is incorporated in the nucleoside 5-Methylcytidine, 5-methylcytidine. Discovery While trying to isolate the bacterial toxin responsible for tuberculosis, W.G. Ruppel isolated a novel nucleic acid named tuberculinic acid in 1898 from ''Mycobacterium tuberculosis, Tubercle bacillus''. The nucleic acid was found to be unusual, in that it contained in addition to thymine, guanine and cytosine, a methylated nucleotide. In 1925, Treat Baldwin Johnson, Johnson and Coghill successfully detected a minor amount of a methylated cytosi ...
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Super-enhancer
Cell differentiation in multicellular organism A multicellular organism is an organism that consists of more than one cell (biology), cell, unlike unicellular organisms. All species of animals, Embryophyte, land plants and most fungi are multicellular, as are many algae, whereas a few organism ...s with different cell types is determined, in each cell type, by the expression of genes under the regulatory control of typical enhancer (genetics), enhancers and super-enhancers. A Enhancer (genetics), typical enhancer(TE), as illustrated in the top panel of the Figure, is a several hundred base pair region of DNA that can bind transcription factors to sequence motifs on the enhancer. The typical enhancer can come in proximity to its target gene through a large chromosome loop. A Mediator (coactivator), Mediator a complex (consisting of about 26 proteins in an interacting structure) communicates #Enhancer_activation_and_implementation, regulatory signals from the enhancer-located DN ...
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Genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as regulatory sequences (see non-coding DNA), and often a substantial fraction of junk DNA with no evident function. Almost all eukaryotes have mitochondrial DNA, mitochondria and a small mitochondrial genome. Algae and plants also contain chloroplast DNA, chloroplasts with a chloroplast genome. The study of the genome is called genomics. The genomes of many organisms have been Whole-genome sequencing, sequenced and various regions have been annotated. The first genome to be sequenced was that of the virus φX174 in 1977; the first genome sequence of a prokaryote (''Haemophilus influenzae'') was published in 1995; the yeast (''Saccharomyces cerevisiae'') genome was the first eukaryotic genome to be sequenced in 1996. The Human Genome Project ...
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Transgene
A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the phenotype of an organism. ''Transgene'' describes a segment of DNA containing a gene sequence that has been isolated from one organism and is introduced into a different organism. This non-native segment of DNA may either retain the ability to produce RNA or protein in the transgenic organism or alter the normal function of the transgenic organism's genetic code. In general, the DNA is incorporated into the organism's germ line. For example, in higher vertebrates this can be accomplished by injecting the foreign DNA into the cell nucleus, nucleus of a fertilized ovum. This technique is routinely used to introduce human disease genes or other genes of interest into strains of Laboratory mouse, laboratory mice to study the function or pathol ...
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