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Extrachromosomal RDNA Circle
Extrachromosomal rDNA circles (aka ERC) are pieces of extrachromosomal circular DNA (eccDNA) derived from ribosomal DNA (rDNA). Initially found in baker's yeast, these self-replicating circles are suggested to contribute to their aging and found in their aged cells. Like ordinar eccDNA, they are created by intra-molecular homologous recombination of the chromosome. The process for intra-molecular homologous recombination is independent of chromosomal replication. The de novo generated circles had exact multiples of tandem copies of 2-kb fragments from cosmid templates. The tandem organization is essential to circle formation. Looping out of organized ribosomal genes in intergenic nontranscribed spacers yielded either large or small repeat circles dependent on large or short repeats of the spacer. In yeast strains The Sgs1 gene mutations in yeast mother cells were shown to have accelerated aging, suggesting their function to cellular senescence. ERCs accumulate in old cells and ...
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Extrachromosomal Circular DNA
Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA structure that was first discovered in 1964 by Alix Bassel and Yasuo Hotta. In contrast to previously identified circular DNA structures (e.g., bacterial plasmids, mitochondrial DNA, circular bacterial chromosomes, or chloroplast DNA), eccDNA are circular DNA found in the eukaryotic nuclei of plant and animal (including human) cells. Extrachromosomal circular DNA is derived from chromosomal DNA, can range in size from 50 base pairs to several mega-base pairs in length, and can encode regulatory elements and full-length genes. eccDNA has been observed in various eukaryotic species and it is proposed to be a byproduct of programmed DNA recombination events, such as V(D)J recombination. Historical Background In 1964, Bassel and Hotta published their initial discovery of eccDNA that they made while researching Franklin Stahl’s chromosomal theory. In their experiments, they visualized isolated whea ...
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Yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitute 1% of all described fungal species. Yeasts are unicellular organisms that evolved from multicellular ancestors, with some species having the ability to develop multicellular characteristics by forming strings of connected budding cells known as pseudohyphae or false hyphae. Yeast sizes vary greatly, depending on species and environment, typically measuring 3–4  µm in diameter, although some yeasts can grow to 40 µm in size. Most yeasts reproduce asexually by mitosis, and many do so by the asymmetric division process known as budding. With their single-celled growth habit, yeasts can be contrasted with molds, which grow hyphae. Fungal species that can take both forms (depending on temperature or other conditions) are ca ...
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Senescence
Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence involves an increase in death rates and/or a decrease in fecundity with increasing age, at least in the latter part of an organism's life cycle. Senescence is the inevitable fate of almost all multicellular organisms with germ-soma separation, but it can be delayed. The discovery, in 1934, that calorie restriction can extend lifespan by 50% in rats, and the existence of species having negligible senescence and potentially immortal organisms such as '' Hydra'', have motivated research into delaying senescence and thus age-related diseases. Rare human mutations can cause accelerated aging diseases. Environmental factors may affect aging – for example, overexposure to ultraviolet radiation accelerates skin aging. Different parts of the body ...
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Retrograde Signaling
Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, instead of signals leaving the nucleus, they are sent to the nucleus. In cell biology, this type of signaling typically occurs between the mitochondria or chloroplast and the nucleus. Signaling molecules from the mitochondria or chloroplast act on the nucleus to affect nuclear gene expression. In this regard, the chloroplast or mitochondria act as a sensor for internal external stimuli which activate a signaling pathway. In neuroscience, retrograde signaling (or retrograde neurotransmission) refers more specifically to the process by which a retrograde messenger, such as anandamide or nitric oxide, is released by a postsynaptic dendrite or cell body, and travels "backwards" across a chemical synapse to bind to the axon terminal of a pre ...
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Xenopus
''Xenopus'' () (Gk., ξενος, ''xenos''=strange, πους, ''pous''=foot, commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known species of this genus are ''Xenopus laevis'' and ''Xenopus tropicalis'', which are commonly studied as model organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects. The genus is also known for its polyploidy, with some species having up to 12 sets of chromosomes. Characteristics ''Xenopus laevis'' is a rather inactive creature. It is incredibly hardy and can live up to 15 years. At times the ponds that ''Xenopus laevis'' is found in dry up, compelling it, in the dry season, to burrow into the mud, leaving a tunnel for air. It may lie dormant for up to a year. If the pond dries up in the rainy season, ''Xenopus laevis'' may migrate long distances to another pond, main ...
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Petite Mutation
petite (ρ–) is a mutant first discovered in the yeast ''Saccharomyces cerevisiae''. Due to the defect in the respiratory chain, 'petite' yeast are unable to grow on media containing only non-fermentable carbon sources (such as glycerol or ethanol) and form small colonies when grown in the presence of fermentable carbon sources (such as glucose). The petite phenotype can be caused by the absence of, or mutations in, mitochondrial DNA (termed "cytoplasmic Petites"), or by mutations in nuclear-encoded genes involved in oxidative phosphorylation. A neutral petite produces all wild type The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ... progeny when crossed with wild type. petite mutations can be induced using a variety of mutagens, including DNA intercalating agents, as well as che ...
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Werner Syndrome Helicase
Werner syndrome ATP-dependent helicase, also known as DNA helicase, RecQ-like type 3, is an enzyme that in humans is encoded by the WRN gene. WRN is a member of the RecQ Helicase family. Helicase enzymes generally unwind and separate double-stranded DNA. These activities are necessary before DNA can be copied in preparation for cell division (DNA replication). Helicase enzymes are also critical for making a blueprint of a gene for protein production, a process called transcription. Further evidence suggests that Werner protein plays a critical role in repairing DNA. Overall, this protein helps maintain the structure and integrity of a person's DNA. The WRN gene is located on the short (p) arm of chromosome 8 between positions 12 and 11.2, from base pair 31,010,319 to base pair 31,150,818. Structure and function WRN is a member of the RecQ Helicase family. It is the only RecQ Helicase that contains 3' to 5' exonuclease activity. These exonuclease activities include degradation ...
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Cellular Senescence
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approximately 50 cell population doublings before becoming senescent. This process is known as "replicative senescence", or the Hayflick limit. Hayflick's discovery of mortal cells paved the path for the discovery and understanding of cellular aging molecular pathways. Cellular senescence can be initiated by a wide variety of stress inducing factors. These stress factors include both environmental and internal damaging events, abnormal cellular growth, oxidative stress, autophagy factors, among many other things. The physiological importance for cell senescence has been attributed to prevention of carcinogenesis, and more recently, aging, development, and tissue repair. Senescent cells contribute to the aging phenotype, including frailty syndrom ...
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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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Mutation
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 source o ...
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Sgs1
Sgs1, also known as slow growth suppressor 1, is a DNA helicase protein found in ''Saccharomyces cerevisiae''. It is a homolog of the bacterial RecQ helicase. Like the other members of the RecQ helicase family, Sgs1 is important for DNA repair. In particular, Sgs1 collaborates with other proteins to repair double-strand breaks during homologous recombination in eukaryotes. Meiosis The Sgs1(BLM) helicase is an ortholog of the human Bloom syndrome protein. It appears to be a central regulator of most of the recombination events that occur during ''S. cerevisiae'' meiosis. During normal meiosis Sgs1(BLM) is responsible for directing recombination towards the alternate formation of either early non-crossover recombinants (NCOs) or Holliday junction joint molecules, the latter being subsequently resolved as crossovers (COs) (see Figure). The several roles of Sgs1 in meiotic recombination were reviewed by Klein and Symington. Primarily, Sgs1 displaces the strand invasion interm ...
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