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Journal ArticleDOI

Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase.

01 Jan 1985-The EMBO Journal (European Molecular Biology Organization)-Vol. 4, Iss: 1, pp 77-84
TL;DR: The unusual splice junction is functional in vivo since it was detected in both alleles of the SOD‐1 gene, which were defined by differences in the length of restriction endonuclease fragments (RFLPs) that hybridize to the cDNA probe.
Abstract: The SOD-1 gene on chromosome 21 and approximately 100 kb of chromosomal DNA from the 21q22 region have been isolated and characterized. The gene which is present as a single copy per haploid genome spans 11 kb of chromosomal DNA. Heteroduplex analysis and DNA sequencing reveals five rather small exons and four introns that interrupt the coding region. The donor sequence at the first intron contains an unusual variant dinucleotide 5'-G-C, rather than the highly conserved 5'-GT. The unusual splice junction is functional in vivo since it was detected in both alleles of the SOD-1 gene, which were defined by differences in the length of restriction endonuclease fragments (RFLPs) that hybridize to the cDNA probe. Genomic blots of human DNA isolated from cells trisomic for chromosome 21 (Down's syndrome patients) show the normal pattern of bands. At the 5' end of gene there are the 'TATA' and 'CAT' promoter sequences as well as four copies of the -GGCGGG- hexanucleotide. Two of these -GC- elements are contained within a 13 nucleotide inverted repeat that could form a stem-loop structure with stability of -33 kcal. The 3'-non coding region of the gene contains five short open reading-frames starting with ATG and terminating with stop codons.
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Journal ArticleDOI
01 May 1986-Nature
TL;DR: It is likely that most vertebrate genes are associated with ‘HTF islands’—DNA sequences in which CpG is abundant and non-methylated; however, highly tissue-specific genes, though, usually lack islands.
Abstract: It is likely that most vertebrate genes are associated with 'HTF islands'--DNA sequences in which CpG is abundant and non-methylated. Highly tissue-specific genes, though, usually lack islands. The contrast between islands and the remainder of the genome may identify sequences that are to be constantly available in the nucleus. DNA methylation appears to be involved in this function, rather than with activation of tissue specific genes.

3,673 citations

Journal ArticleDOI
TL;DR: It is shown that CpG islands in methylated genomes are maintained, despite a tendency for 5mCpG to mutate by deamination to TpG+CpA, by the structural stability of a high G+C content alone, and that C pG islands associated with exons result from some selective importance of the arginine codon CGX.

3,321 citations

Journal ArticleDOI
TL;DR: Three unique and highly compartmentalized mammalian superoxide dismutases have been biochemically and molecularly characterized to date and a molecular understanding of each of these genes has proven useful toward the deciphering of their biological roles.

1,870 citations


Cites background or methods from "Architecture and anatomy of the chr..."

  • ...Data for this figure was extracted from the following sources: SOD1 [21], SOD2 [26], and SOD3 [32]....

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  • ...The SOD1 gene has been localized to chromosome 21 (region 21q22) in humans [21], chromosome 1 (1q123 14) in bovine species [39], and chromosome 16 (region 16B43 ter) in the mouse [40]....

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  • ...The genomic sequence for SOD1 has been identified in the rat [18,19], mouse [20], and human [21]....

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Journal ArticleDOI
TL;DR: The role of each SOD in vascular biologies, physiologies, and pathophysiologies such as atherosclerosis, hypertension, and angiogenesis is updated and the importance of metal cofactors in the activity of SODs is discussed.
Abstract: Excessive reactive oxygen species Revised abstract, especially superoxide anion (O2•−), play important roles in the pathogenesis of many cardiovascular diseases, including hypertension and atherosclerosis Superoxide dismutases (SODs) are the major antioxidant defense systems against O2•−, which consist of three isoforms of SOD in mammals: the cytoplasmic Cu/ZnSOD (SOD1), the mitochondrial MnSOD (SOD2), and the extracellular Cu/ZnSOD (SOD3), all of which require catalytic metal (Cu or Mn) for their activation Recent evidence suggests that in each subcellular location, SODs catalyze the conversion of O2•− H2O2, which may participate in cell signaling In addition, SODs play a critical role in inhibiting oxidative inactivation of nitric oxide, thereby preventing peroxynitrite formation and endothelial and mitochondrial dysfunction The importance of each SOD isoform is further illustrated by studies from the use of genetically altered mice and viral-mediated gene transfer Given the essential role

1,464 citations


Cites background from "Architecture and anatomy of the chr..."

  • ...Second, the amino terminal residues [96–193] contain active site, showing about 50% homology to SOD1....

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Journal ArticleDOI
TL;DR: Studies in model organisms and humans are discussed, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling and the need for fine local control of ROS signaling.
Abstract: Superoxide dismutases (SODs) are universal enzymes of organisms that live in the presence of oxygen. They catalyze the conversion of superoxide into oxygen and hydrogen peroxide. Superoxide anions are the intended product of dedicated signaling enzymes as well as the byproduct of several metabolic processes including mitochondrial respiration. Through their activity, SOD enzymes control the levels of a variety of reactive oxygen species (ROS) and reactive nitrogen species, thus both limiting the potential toxicity of these molecules and controlling broad aspects of cellular life that are regulated by their signaling functions. All aerobic organisms have multiple SOD proteins targeted to different cellular and subcellular locations, reflecting the slow diffusion and multiple sources of their substrate superoxide. This compartmentalization also points to the need for fine local control of ROS signaling and to the possibility for ROS to signal between compartments. In this review, we discuss studies in model organisms and humans, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling.

903 citations


Cites background from "Architecture and anatomy of the chr..."

  • ...Three classes of SOD have evolved in various organisms possessing different catalytic metal ions: Cu/Zn SODs, Mn SOD/Fe SODs, and Ni SODs (Table S1; Levanon et al., 1985; Campbell et al., 1986; Chang et al., 1988; Wan et al., 1994; Jones et al., 1995; Strålin et al., 1995; Duttaroy et al., 1997; Folz et al., 1997; Antonyuk et al., 2009; Jung et al., 2011; Blackney et al., 2014)....

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