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. 1983 Sep;80(18):5465–5469. doi: 10.1073/pnas.80.18.5465

Nucleotide sequence and expression of human chromosome 21-encoded superoxide dismutase mRNA.

L Sherman, N Dafni, J Lieman-Hurwitz, Y Groner
PMCID: PMC384278  PMID: 6577438

Abstract

Cytoplasmic superoxide dismutase (SOD-1; EC 1.15.1.1) is encoded by human chromosome 21. The SOD-1 gene locus is located at chromosomal region 21q22, which is involved in Down syndrome. cDNA clones containing sequences of human SOD-1 were previously isolated. In the present study the nucleotide sequence of one clone, designated pS61-10, was determined. It contains 459 nucleotides representing the entire coding region and 95 nucleotides of the 3' untranslated region. In human cells two poly(A)-containing SOD-1 RNAs of 0.7 and 0.5 kilobases were detected. These two species are also present in monkey cells, whereas mouse cells contain only a 0.5-kilobase RNA. In a mouse/human hybrid line that contains chromosome 21 as the only human chromosome, the two human SOD-1 RNAs were detected, indicating that both are encoded by this chromosome. These RNAs were found in poly(A)-containing polysomal RNA and were translated in vitro to SOD-1 polypeptide; they are therefore functional mRNAs. In normal human fibroblasts 0.002-0.006% of the poly(A)-containing RNA was SOD-1 RNA. The level in monosomic 21 cells was 70% of this value and the level in fibroblasts from Down syndrome patients was about 2 times higher than normal.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barra D., Martini F., Bannister J. V., Schininà M. E., Rotilio G., Bannister W. H., Bossa F. The complete amino acid sequence of human Cu/Zn superoxide dismutase. FEBS Lett. 1980 Oct 20;120(1):53–56. doi: 10.1016/0014-5793(80)81044-1. [DOI] [PubMed] [Google Scholar]
  2. Briggs R. G., Fee J. A. Further characterization of human erythrocyte superoxide dismutase. Biochim Biophys Acta. 1978 Nov 20;537(1):86–99. doi: 10.1016/0005-2795(78)90605-0. [DOI] [PubMed] [Google Scholar]
  3. Canaani D., Kahana C., Lavi S., Groner Y. Identification and mapping of N6-methyladenosine containing sequences in simian virus 40 RNA. Nucleic Acids Res. 1979 Jun 25;6(8):2879–2899. doi: 10.1093/nar/6.8.2879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
  5. Crosti N., Serra A., Rigo A., Viglino P. Dosage effect of SOD-A gene in 21-trisomic cells. Hum Genet. 1976 Feb 29;31(2):197–202. doi: 10.1007/BF00296146. [DOI] [PubMed] [Google Scholar]
  6. Feaster W. W., Kwok L. W., Epstein C. J. Dosage effects for superoxide dismutase-1 in nucleated cells aneuploid for chromosome 21. Am J Hum Genet. 1977 Nov;29(6):563–570. [PMC free article] [PubMed] [Google Scholar]
  7. Frants R. R., Eriksson A. W., Jongbloet P. H., Hamers A. J. Letter: Superoxide dismutase in Down syndrome. Lancet. 1975 Jul 5;2(7923):42–43. doi: 10.1016/s0140-6736(75)92996-7. [DOI] [PubMed] [Google Scholar]
  8. Fridovich I. Superoxide dismutases. Annu Rev Biochem. 1975;44:147–159. doi: 10.1146/annurev.bi.44.070175.001051. [DOI] [PubMed] [Google Scholar]
  9. Fridovich I. The biology of oxygen radicals. Science. 1978 Sep 8;201(4359):875–880. doi: 10.1126/science.210504. [DOI] [PubMed] [Google Scholar]
  10. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gluzman Y. SV40-transformed simian cells support the replication of early SV40 mutants. Cell. 1981 Jan;23(1):175–182. doi: 10.1016/0092-8674(81)90282-8. [DOI] [PubMed] [Google Scholar]
  12. Goeddel D. V., Leung D. W., Dull T. J., Gross M., Lawn R. M., McCandliss R., Seeburg P. H., Ullrich A., Yelverton E., Gray P. W. The structure of eight distinct cloned human leukocyte interferon cDNAs. Nature. 1981 Mar 5;290(5801):20–26. doi: 10.1038/290020a0. [DOI] [PubMed] [Google Scholar]
  13. Hagemeijer A., Smit E. M. Partial trisomy 21. Further evidence that trisomy of band 21q22 is essential for Down's phenotype. Hum Genet. 1977 Aug 31;38(1):15–23. doi: 10.1007/BF00295803. [DOI] [PubMed] [Google Scholar]
  14. Hagenbüchle O., Bovey R., Young R. A. Tissue-specific expression of mouse-alpha-amylase genes: nucleotide sequence of isoenzyme mRNAs from pancreas and salivary gland. Cell. 1980 Aug;21(1):179–187. doi: 10.1016/0092-8674(80)90125-7. [DOI] [PubMed] [Google Scholar]
  15. Heidecker G., Messing J., Gronenborn B. A versatile primer for DNA sequencing in the M13mp2 cloning system. Gene. 1980 Jun;10(1):69–73. doi: 10.1016/0378-1119(80)90145-6. [DOI] [PubMed] [Google Scholar]
  16. Jabusch J. R., Farb D. L., Kerschensteiner D. A., Deutsch H. F. Some sulfhydryl properties and primary structure of human erythrocyte superoxide dismutase. Biochemistry. 1980 May 27;19(11):2310–2316. doi: 10.1021/bi00552a005. [DOI] [PubMed] [Google Scholar]
  17. Jung A., Sippel A. E., Grez M., Schütz G. Exons encode functional and structural units of chicken lysozyme. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5759–5763. doi: 10.1073/pnas.77.10.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kozak C. A., Lawrence J. B., Ruddle F. H. A sequential staining technique for the chromosomal analysis of the interspecific mouse/hamster and mouse/human somatic cell hybrids. Exp Cell Res. 1977 Mar 1;105(1):109–117. doi: 10.1016/0014-4827(77)90156-2. [DOI] [PubMed] [Google Scholar]
  20. Kurnit D. M. Down syndrome: gene dosage at the transcriptional level in skin fibroblasts. Proc Natl Acad Sci U S A. 1979 May;76(5):2372–2375. doi: 10.1073/pnas.76.5.2372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. LEJEUNE J., GAUTIER M., TURPIN R. Etude des chromosomes somatiques de neuf enfants mongoliens. C R Hebd Seances Acad Sci. 1959 Mar 16;248(11):1721–1722. [PubMed] [Google Scholar]
  22. Leicht M., Long G. L., Chandra T., Kurachi K., Kidd V. J., Mace M., Jr, Davie E. W., Woo S. L. Sequence homology and structural comparison between the chromosomal human alpha 1-antitrypsin and chicken ovalbumin genes. Nature. 1982 Jun 24;297(5868):655–659. doi: 10.1038/297655a0. [DOI] [PubMed] [Google Scholar]
  23. Lieman-Hurwitz J., Dafni N., Lavie V., Groner Y. Human cytoplasmic superoxide dismutase cDNA clone: a probe for studying the molecular biology of Down syndrome. Proc Natl Acad Sci U S A. 1982 May;79(9):2808–2811. doi: 10.1073/pnas.79.9.2808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Marklund S. L. Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7634–7638. doi: 10.1073/pnas.79.24.7634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  26. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  27. Moore E. E., Jones C., Kao F. T., Oates D. C. Synteny between glycinamide ribonucleotide synthetase and superoxide dismutase (soluble). Am J Hum Genet. 1977 Jul;29(4):389–396. [PMC free article] [PubMed] [Google Scholar]
  28. Niebuhr E. Down's syndrome. The possibility of a pathogenetic segment on chromosome no. 21. Humangenetik. 1974 Jan 22;21(1):99–101. doi: 10.1007/BF00278575. [DOI] [PubMed] [Google Scholar]
  29. Palacios R., Palmiter R. D., Schimke R. T. Identification and isolation of ovalbumin-synthesizing polysomes. I. Specific binding of 125 I-anti-ovalbumin to polysomes. J Biol Chem. 1972 Apr 25;247(8):2316–2321. [PubMed] [Google Scholar]
  30. Patterson D., Graw S., Jones C. Demonstration, by somatic cell genetics, of coordinate regulation of genes for two enzymes of purine synthesis assigned to human chromosome 21. Proc Natl Acad Sci U S A. 1981 Jan;78(1):405–409. doi: 10.1073/pnas.78.1.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Proudfoot N. The end of the message. Nature. 1982 Aug 5;298(5874):516–517. doi: 10.1038/298516a0. [DOI] [PubMed] [Google Scholar]
  32. Rotter V., Boss M. A., Baltimore D. Increased concentration of an apparently identical cellular protein in cells transformed by either Abelson murine leukemia virus or other transforming agents. J Virol. 1981 Apr;38(1):336–346. doi: 10.1128/jvi.38.1.336-346.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  34. Sichitiu S., Sinet P. M., Lejeune J., Frézal J. Surdosage de la forme dimérique de l'indophénoloxydase dans la trisomie 21, secondaire au surdosage génique. Humangenetik. 1974 Jun 26;23(1):65–72. doi: 10.1007/BF00295684. [DOI] [PubMed] [Google Scholar]
  35. Sinet P. M., Allard D., Lejeune J., Jérôme H. Augmentation d'activité de la superoxyde dismutase érythrocytaire dans la trisomie pour le chromosome 21. C R Acad Sci Hebd Seances Acad Sci D. 1974 Jun 17;278(25):3267–3270. [PubMed] [Google Scholar]
  36. Sinet P. M., Couturier J., Dutrillaux B., Poissonnier M., Raoul O., Rethore M. O., Allard D., Lejeune J., Jerome H. Trisomie 21 et superoxyde dismutase-1 (IPO-A). Tentative de localisation sur la sous bande 21Q22.1. Exp Cell Res. 1976 Jan;97:47–55. doi: 10.1016/0014-4827(76)90653-4. [DOI] [PubMed] [Google Scholar]
  37. Sood A. K., Pereira D., Weissman S. M. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981 Jan;78(1):616–620. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  39. Tan Y. H., Tischfield J., Ruddle F. H. The linkage of genes for the human interferon-induced antiviral protein and indophenol oxidase-B traits to chromosome G-21. J Exp Med. 1973 Feb 1;137(2):317–330. doi: 10.1084/jem.137.2.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Todaro G. J., Green H., Swift M. R. Susceptibility of human diploid fibroblast strains to transformation by SV40 virus. Science. 1966 Sep 9;153(3741):1252–1254. doi: 10.1126/science.153.3741.1252. [DOI] [PubMed] [Google Scholar]
  41. Van Hemmen J. J., Meuling W. J. Inactivation of biologically active DNA by gamma-ray-induced superoxide radicals and their dismutation products singlet molecular oxygen and hydrogen peroxide. Biochim Biophys Acta. 1975 Aug 21;402(2):133–141. doi: 10.1016/0005-2787(75)90031-3. [DOI] [PubMed] [Google Scholar]
  42. Vora S., Francke U. Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3738–3742. doi: 10.1073/pnas.78.6.3738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Weisiger R. A., Fridovich I. Superoxide dismutase. Organelle specificity. J Biol Chem. 1973 May 25;248(10):3582–3592. [PubMed] [Google Scholar]
  44. Weissenbach J., Zeevi M., Landau T., Revel M. Identification of the translation products of human fibroblast interferon mRNA in reticulocyte lysates. Eur J Biochem. 1979 Jul;98(1):1–8. doi: 10.1111/j.1432-1033.1979.tb13153.x. [DOI] [PubMed] [Google Scholar]
  45. Williams J. D., Summitt R. L., Martens P. R., Kimbrell R. A. Familial Down syndrome due to t(10;21) translocation: evidence that the Down phenotype is related to trisomy of a specific segment of chromosome 21. Am J Hum Genet. 1975 Jul;27(4):478–485. [PMC free article] [PubMed] [Google Scholar]
  46. van Someren H., Westerveld A., Hagemeijer A., Mees J. R., Meera Khan P., Zaalberg O. B. Human antigen and enzyme markers in man-Chinese hamster somatic cell hybrids: evidence for synteny between the HL-A, PGM3, ME1, and IPO-B loci. Proc Natl Acad Sci U S A. 1974 Mar;71(3):962–965. doi: 10.1073/pnas.71.3.962. [DOI] [PMC free article] [PubMed] [Google Scholar]

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