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8-oxo-2'-deoxyguanosine
8-Oxo-2'-deoxyguanosine (8-oxo-dG) is an oxidized derivative of deoxyguanosine. 8-Oxo-dG is one of the major products of DNA oxidation. Concentrations of 8-oxo-dG within a cell are a measurement of oxidative stress. In DNA Steady-state levels of DNA damages represent the balance between formation and repair. Swenberg et al. measured average frequencies of steady state endogenous DNA damages in mammalian cells. The most frequent oxidative DNA damage normally present in DNA is 8-oxo-dG, occurring at an average frequency of 2,400 per cell. When 8-oxo-dG is induced by a DNA damaging agent it is rapidly repaired. For example, 8-oxo-dG was increased 10-fold in the livers of mice subjected to ionizing radiation, but the excess 8-oxo-dG was rapidly removed with a half-life of 11 minutes. As reviewed by Valavanidis et al. increased levels of 8-oxo-dG in a tissue can serve as a biomarker of oxidative stress. They also noted that increased levels of 8-oxo-dG are frequently found d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Oxidation
DNA oxidation is the process of oxidative damage of deoxyribonucleic acid. As described in detail by Burrows et al., 8-oxo-2'-deoxyguanosine (8-oxo-dG) is the most common oxidative lesion observed in duplex DNA because guanine has a lower one-electron reduction potential than the other nucleosides in DNA. The one electron reduction potentials of the nucleosides (in volts versus NHE) are guanine 1.29, adenine 1.42, cytosine 1.6 and thymine 1.7. About 1 in 40,000 guanines in the genome are present as 8-oxo-dG under normal conditions. This means that >30,000 8-oxo-dGs may exist at any given time in the genome of a human cell. Another product of DNA oxidation is 8-oxo-dA. 8-oxo-dA occurs at about 1/10 the frequency of 8-oxo-dG. The reduction potential of guanine may be reduced by as much as 50%, depending on the particular neighboring nucleosides stacked next to it within DNA. Excess DNA oxidation is linked to certain diseases and cancers, while normal levels of oxidized nucleo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epigenetics In Learning And Memory
While the cellular and molecular mechanisms of learning and memory have long been a central focus of neuroscience, it is only in recent years that attention has turned to the epigenetic mechanisms behind the dynamic changes in gene transcription responsible for memory formation and maintenance. Epigenetic gene regulation often involves the physical marking (chemical modification) of DNA or associated proteins to cause or allow long-lasting changes in gene activity. Epigenetic mechanisms such as DNA methylation and histone modifications (methylation, acetylation, and deacetylation) have been shown to play an important role in learning and memory. DNA Methylation DNA methylation involves the addition of a methyl group to a 5' cytosine residue. This usually occurs at cytosines that form part of a cytosine-guanine dinucleotide (CpG sites). Methylation can lead to activation or repression of gene transcription and is mediated through the activity of DNA methyltransferases (DNMTs). DNM ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from oxidative metabolism causes base damage, as well as strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O2− ( superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the development of attention deficit hyperactivity disorder, cancer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Damage
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 mali ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CpG Site
The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG islands (or CG islands). Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosines. Enzymes that add a methyl group are called DNA methyltransferases. In mammals, 70% to 80% of CpG cytosines are methylated. Methylating the cytosine within a gene can change its expression, a mechanism that is part of a larger field of science studying gene regulation that is called epigenetics. Methylated cytosines often mutate to thymines. In humans, about 70% of promoters located near the transcription start site of a gene (proximal promoters) contain a CpG island. CpG characteristics Definition ''CpG'' is shorthand for ''5'—C—phosphate—G—3' '', that is, cytosine and guanine separated by only one phosphate group; phospha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transversion
Transversion, in molecular biology, refers to a point mutation in DNA in which a single (two ring) purine ( A or G) is changed for a (one ring) pyrimidine ( T or C), or vice versa. A transversion can be spontaneous, or it can be caused by ionizing radiation or alkylating agents. It can only be reversed by a spontaneous reversion. Ratio of transitions to transversions Although there are two possible transversions but only one possible transition per base, transition mutations are more likely than transversions because substituting a single ring structure for another single ring structure is more likely than substituting a double ring for a single ring. Also, transitions are less likely to result in amino acid substitutions (due to wobble base pair), and are therefore more likely to persist as "silent substitutions" in populations as single nucleotide polymorphisms (SNPs). A transversion usually has a more pronounced effect than a transition because the third nucleotide ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Demethylation
For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence or, in replicating cells, by preventing addition of methyl groups to DNA so that the replicated DNA will largely have cytosine in the DNA sequence (5mC will be diluted out). Methylated cytosine is frequently present in the linear DNA sequence where a cytosine is followed by a guanine in a 5' → 3' direction (a CpG site). In mammals, DNA methyltransferases (which add methyl groups to DNA bases) exhibit a strong sequence preference for cytosines at CpG sites. There appear to be more than 20 million CpG dinucleotides in the human genome (see genomic distribution). In mammals, on average, 70% to 80% of CpG cytosines are methylated, though the level of methylation varies with different tissues. Methylated cytosines often occur in group ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally, the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by interfering with the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to canc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Damage Theory Of Aging
The DNA damage theory of aging proposes that aging is a consequence of unrepaired accumulation of naturally occurring DNA damage. Damage in this context is a DNA alteration that has an abnormal structure. Although both mitochondrial and nuclear DNA damage can contribute to aging, nuclear DNA is the main subject of this analysis. Nuclear DNA damage can contribute to aging either indirectly (by increasing apoptosis or cellular senescence) or directly (by increasing cell dysfunction). Several review articles have shown that deficient DNA repair, allowing greater accumulation of DNA damage, causes premature aging; and that increased DNA repair facilitates greater longevity. Mouse models of nucleotide-excision–repair syndromes reveal a striking correlation between the degree to which specific DNA repair pathways are compromised and the severity of accelerated aging, strongly suggesting a causal relationship. Human population studies show that single-nucleotide polymorphisms in DNA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thymidine Kinase
Thymidine kinase is an enzyme, a phosphotransferase (a kinase): 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21. It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2. Certain viruses also have genetic information for expression of viral thymidine kinases. Thymidine kinase catalyzes the reaction: :Thd + ATP → TMP + ADP where Thd is (deoxy)thymidine, ATP is adenosine triphosphate, TMP is (deoxy) thymidine monophosphate and ADP is adenosine diphosphate. Thymidine kinases have a key function in the synthesis of DNA and therefore in cell division, as they are part of the unique reaction chain to introduce thymidine into the DNA. Thymidine is present in the body fluids as a result of degradation of DNA from food and from dead cells. Thymidine kinase is required for the action of many antiviral drugs. It is used to select hybridoma cell lines in production of monoclonal antibodies. In clinical chemistry it is u ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Deoxyguanosine
Deoxyguanosine is composed of the purine nucleobase guanine linked by its N9 nitrogen to the C1 carbon of deoxyribose. It is similar to guanosine, but with one hydroxyl group removed from the 2' position of the ribose sugar (making it deoxyribose). If a phosphate group is attached at the 5' position, it becomes deoxyguanosine monophosphate Deoxyguanosine monophosphate (dGMP), also known as deoxyguanylic acid or deoxyguanylate in its conjugate acid and conjugate base forms, respectively, is a derivative of the common nucleic acid guanosine triphosphate (GTP), in which the –OH (hydro .... Deoxyguanosine is one of the four deoxyribonucleosides that make up DNA. See also * 8-Oxo-2'-deoxyguanosine References Nucleosides Purines Hydroxymethyl compounds {{Biochemistry-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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