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Sirt7
NAD-dependent deacetylase sirtuin 7 is an enzyme that in humans is encoded by the ''SIRT7'' gene. SIRT7 is member of the mammalian sirtuin family of proteins, which are homologs to the yeast Sir2 protein. Function SIRT7 facilitates the transcription of DNA by DNA polymerase I, DNA polymerase II, and DNA polymerase III. In humans cells, SIRT7 has only been shown to interact with two other molecules: RNA polymerase I (RNA Pol I) and upstream binding factor (UBF). SIRT7 is localized to the nucleolus and interacts with RNA Pol I. Chromatin immunoprecipitation studies demonstrate that SIRT7 localizes to rDNA, and coimmunoprecipitation shows that SIRT7 binds RNA Pol I. In addition SIRT7 interacts with UBF, a major component of the RNA Pol I initiation complex. It is not known whether or not SIRT7 is modifying RNA Pol I and/or UBF, and if so, what those modifications are. SIRT7 is expressed more in metabolically active tissues, such as liver and spleen, and less in non-proliferating ...
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Sirtuin
Sirtuins are a family of signaling proteins involved in metabolic regulation. They are ancient in animal evolution and appear to possess a highly conserved structure throughout all kingdoms of life. Chemically, sirtuins are a class of proteins that possess either mono- ADP-ribosyltransferase or deacylase activity, including deacetylase, desuccinylase, demalonylase, demyristoylase and depalmitoylase activity. The name Sir2 comes from the yeast gene 'silent mating-type information regulation 2', the gene responsible for cellular regulation in yeast. From ''in vitro'' studies, sirtuins are implicated in influencing cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy efficiency and alertness during low-calorie situations. As of 2018, there was no clinical evidence that sirtuins affect human aging. Yeast Sir2 and some, but not all, sirtuins are protein deacetylases. Unlike other known protein deacetylases, which simply hyd ...
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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 reaction ra ...
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Ribosomal DNA
Ribosomal DNA (rDNA) is a DNA sequence that codes for ribosomal RNA. These sequences regulate transcription initiation and amplification, and contain both transcribed and non-transcribed spacer segments. In the human genome there are 5 chromosomes with nucleolus organizer regions: the acrocentric chromosomes 13 (RNR1), 14 ( RNR2), 15 ( RNR3), 21 (RNR4) and 22 (RNR5). The genes that are responsible for encoding the various sub-units of rRNA are located across multiple chromosomes in humans. But the genes that encode for rRNA are highly conserved across the domains, with only the copy numbers involved for the genes having varying numbers per species. In Bacteria, Archaea, and chloroplasts the rRNA is composed of different (smaller) units, the large (23S) ribosomal RNA, 16S ribosomal RNA and 5S rRNA. The 16S rRNA is widely used for phylogenetic studies. Eukaryotes The rRNA transcribed from the approximately 600 rDNA repeats forms the most abundant section of RNA found in cells ...
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Progeroid Syndromes
Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term ''progeroid syndrome'' does not necessarily imply progeria (Hutchinson–Gilford progeria syndrome), which is a specific type of progeroid syndrome. ''Progeroid'' means "resembling premature aging," a definition that can apply to a broad range of diseases. Familial Alzheimer's disease and familial Parkinson's disease are two well-known accelerated-aging diseases that are more frequent in older individuals. They affect only one tissue and can be classified as unimodal progeroid syndromes. Segmental progeria, which is more frequently associated with the term ''progeroid syndrome,'' tends to affect multiple or all tissues while causing affected individuals to exhibit only some of the features associated with aging. All disorders within this group are thought to be monogenic, meaning they arise from mutations of a single ...
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Science (journal)
''Science'', also widely referred to as ''Science Magazine'', is the peer-reviewed academic journal of the American Association for the Advancement of Science (AAAS) and one of the world's top academic journals. It was first published in 1880, is currently circulated weekly and has a subscriber base of around 130,000. Because institutional subscriptions and online access serve a larger audience, its estimated readership is over 400,000 people. ''Science'' is based in Washington, D.C., United States, with a second office in Cambridge, UK. Contents The major focus of the journal is publishing important original scientific research and research reviews, but ''Science'' also publishes science-related news, opinions on science policy and other matters of interest to scientists and others who are concerned with the wide implications of science and technology. Unlike most scientific journals, which focus on a specific field, ''Science'' and its rival ''Nature (journal), Nature'' c ...
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Homologous Recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be also RNA in viruses). Homologous recombination is widely used by cells to accurately DNA repair harmful breaks that occur on both strands of DNA, known as double-strand breaks (DSB), in a process called homologous recombinational repair (HRR). Homologous recombination also produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and egg cells in animals. These new combinations of DNA represent genetic variation in offspring, which in turn enables populations to adapt during the course of evolution. Homologous recombination is also used in horizontal gene transfer to exchange genetic material between different strains and species of bacteria and viruses. Horizontal ...
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Gene Expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in 1958, further developed in his 1970 article, and expanded by the subsequent discoveries of reverse transcription and RNA replication. The process of gene expression is used by all known life—eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses—to generate the macromolecular machinery for life. In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phenotype, '' ...
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TP53BP1
Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the ''TP53BP1'' gene. Clinical significance 53BP1 is underexpressed in most cases of triple-negative breast cancer. DNA repair DNA double-strand breaks (DSBs) are cytotoxic damages that can be repaired either by the homologous recombinational repair (HR) pathway or by the non-homologous end-joining (NHEJ) pathway. NHEJ, although faster than HR, is less accurate. The early divergent step between the two pathways is end resection, and this step is regulated by numerous factors. In particular, BRCA1 and 53BP1 play a role in determining the balance between the two pathways. 53BP1 restricts resection and promotes NHEJ. Age-associated deficient repair Ordinarily during the G1 phase of the cell cycle, when a sister chromatid is unavailable for HR, NHEJ is the predominant pathway for repairing DNA double-strand breaks (DSBs). However, as individuals age, ...
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Histone H3
Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a string' structure. Histone proteins are highly post-translationally modified however Histone H3 is the most extensively modified of the five histones. The term "Histone H3" alone is purposely ambiguous in that it does not distinguish between sequence variants or modification state. Histone H3 is an important protein in the emerging field of epigenetics, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes. Epigenetics and post-translational modifications The N-terminus of H3 protrudes from the globular nucleosome core and is susceptible to post-translational modification that influence cellular processes. These modifications include the covalent attachment ...
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Acylation
In chemistry, acylation (or alkanoylation) is the chemical reaction in which an acyl group () is added to a compound. The compound providing the acyl group is called the acylating agent. Because they form a strong electrophile when treated with some metal catalysts, acyl halides are commonly used as acylating agents. For example, Friedel–Crafts acylation uses acetyl chloride (ethanoyl chloride or ) as the agent and aluminum chloride () as a catalyst to add an ethanoyl ( acetyl) group to benzene: The mechanism of this reaction is electrophilic aromatic substitution. Acyl halides and acid anhydrides of carboxylic acids are also commonly used acylating agents. In some cases, active esters exhibit comparable reactivity. All react with amines to form amides and with alcohols to form esters by nucleophilic acyl substitution. Acylation can be used to prevent rearrangement reactions that would normally occur in alkylation. To do this an acylation reaction is performed, then the ...
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DNA Damage (naturally Occurring)
DNA damage is an alteration in the chemical structure of DNA, such as a break in a strand of DNA, a nucleobase missing from the backbone of DNA, or a chemically changed base such as 8-OHdG. DNA damage can occur naturally or via environmental factors, but is distinctly different from mutation, although both are types of error in DNA. DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of base pairs. DNA damages cause changes in the structure of the genetic material and prevents the replication mechanism from functioning and performing properly. The DNA damage response (DDR) is a complex signal transduction pathway which recognizes when DNA is damaged and initiates the cellular response to the damage. DNA damage and mutation have different biological consequences. While most DNA damages can undergo DNA repair, such repair is not 100% efficient. Un-repaired DNA damages accumulate in non-replicating cells, such as cells in the brains o ...
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Non-homologous End Joining
Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair(HDR), which requires a homologous sequence to guide repair. NHEJ is active in both non-dividing and proliferating cells, while HDR is not readily accessible in non-dividing cells. The term "non-homologous end joining" was coined in 1996 by Moore and Haber. NHEJ is typically guided by short homologous DNA sequences called microhomologies. These microhomologies are often present in single-stranded overhangs on the ends of double-strand breaks. When the overhangs are perfectly compatible, NHEJ usually repairs the break accurately. Imprecise repair leading to loss of nucleotides can also occur, but is much more common when the overhangs are not compatible. Inappropriate NHEJ can lead to translocations and telomere fusion, hallmarks ...
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