Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Oct 1, 1991; 88(19): 8460–8464.

A human nuclear uracil DNA glycosylase is the 37-kDa subunit of glyceraldehyde-3-phosphate dehydrogenase.


We have isolated and characterized a plasmid (pChug 20.1) that contains the cDNA of a nuclear uracil DNA glycosylase (UDG) gene isolated from normal human placenta. This cDNA directed the synthesis of a fusion protein (Mr 66,000) that exhibited UDG activity. The enzymatic activity was specific for a uracil-containing polynucleotide substrate and was inhibited by a glycosylase antibody or a beta-galactosidase antibody. Sequence analysis demonstrated an open reading frame that encoded a protein of 335 amino acids of calculated Mr 36,050 and pI 8.7, corresponding to the Mr 37,000 and pI 8.1 of purified human placental UDG. No homology was seen between this cDNA and the UDG of herpes simplex virus, Escherichia coli, and yeast; nor was there homology with the putative human mitochondrial UDG cDNA or with a second human nuclear UDG cDNA. Surprisingly, a search of the GenBank data base revealed that the cDNA of UDG was completely homologous with the 37-kDa subunit of human glyceraldehyde-3-phosphate dehydrogenase. Human erythrocyte glyceraldehyde-3-phosphate dehydrogenase was obtained commercially in its tetrameric form. A 37-kDa subunit was isolated from it and shown to possess UDG activity equivalent to that seen for the purified human placental UDG. The multiple functions of this 37-kDa protein as here and previously reported indicate that it possesses a series of activities, depending on its oligomeric state. Accordingly, mutation(s) in the gene of this multifunctional protein may conceivably result in the diverse cellular phenotypes of Bloom syndrome.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bessman MJ, Lehman IR, Adler J, Zimmerman SB, Simms ES, Kornberg A. ENZYMATIC SYNTHESIS OF DEOXYRIBONUCLEIC ACID. III. THE INCORPORATION OF PYRIMIDINE AND PURINE ANALOGUES INTO DEOXYRIBONUCLEIC ACID. Proc Natl Acad Sci U S A. 1958 Jul 15;44(7):633–640. [PMC free article] [PubMed]
  • Shapiro R, Klein RS. The deamination of cytidine and cytosine by acidic buffer solutions. Mutagenic implications. Biochemistry. 1966 Jul;5(7):2358–2362. [PubMed]
  • Hayatsu H. Co-operative mutagenic actions of bisulfite and nitrogen nucleophiles. J Mol Biol. 1977 Sep;115(1):19–31. [PubMed]
  • Vollberg TM, Siegler KM, Cool BL, Sirover MA. Isolation and characterization of the human uracil DNA glycosylase gene. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8693–8697. [PMC free article] [PubMed]
  • Seal G, Arenaz P, Sirover MA. Purification and properties of the human placental uracil DNA glycosylase. Biochim Biophys Acta. 1987 Aug 13;925(2):226–233. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Sirover MA. Induction of the DNA repair enzyme uracil-DNA glycosylase in stimulated human lymphocytes. Cancer Res. 1979 Jun;39(6 Pt 1):2090–2095. [PubMed]
  • Varshney U, Hutcheon T, van de Sande JH. Sequence analysis, expression, and conservation of Escherichia coli uracil DNA glycosylase and its gene (ung). J Biol Chem. 1988 Jun 5;263(16):7776–7784. [PubMed]
  • Arenaz P, Sirover MA. Isolation and characterization of monoclonal antibodies directed against the DNA repair enzyme uracil DNA glycosylase from human placenta. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5822–5826. [PMC free article] [PubMed]
  • Olsen LC, Aasland R, Wittwer CU, Krokan HE, Helland DE. Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme. EMBO J. 1989 Oct;8(10):3121–3125. [PMC free article] [PubMed]
  • Muller SJ, Caradonna S. Isolation and characterization of a human cDNA encoding uracil-DNA glycosylase. Biochim Biophys Acta. 1991 Feb 16;1088(2):197–207. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. [PubMed]
  • Percival KJ, Klein MB, Burgers PM. Molecular cloning and primary structure of the uracil-DNA-glycosylase gene from Saccharomyces cerevisiae. J Biol Chem. 1989 Feb 15;264(5):2593–2598. [PubMed]
  • Worrad DM, Caradonna S. Identification of the coding sequence for herpes simplex virus uracil-DNA glycosylase. J Virol. 1988 Dec;62(12):4774–4777. [PMC free article] [PubMed]
  • Arcari P, Martinelli R, Salvatore F. The complete sequence of a full length cDNA for human liver glyceraldehyde-3-phosphate dehydrogenase: evidence for multiple mRNA species. Nucleic Acids Res. 1984 Dec 11;12(23):9179–9189. [PMC free article] [PubMed]
  • Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed]
  • Seal G, Brech K, Karp SJ, Cool BL, Sirover MA. Immunological lesions in human uracil DNA glycosylase: association with Bloom syndrome. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2339–2343. [PMC free article] [PubMed]
  • Weksberg R, Smith C, Anson-Cartwright L, Maloney K. Bloom syndrome: a single complementation group defines patients of diverse ethnic origin. Am J Hum Genet. 1988 Jun;42(6):816–824. [PMC free article] [PubMed]
  • Constantinides SM, Deal WC., Jr Reversible dissociation of tetrameric rabbit muscle glyceraldehyde 3-phosphate dehydrogenase into dimers or monomers by adenosine triphosphate. J Biol Chem. 1969 Oct 25;244(20):5695–5702. [PubMed]
  • FOX JB, Jr, DANDLIKER WB. A study of some of the physical properties of glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 1956 Jan;218(1):53–57. [PubMed]
  • Huitorel P, Pantaloni D. Bundling of microtubules by glyceraldehyde-3-phosphate dehydrogenase and its modulation by ATP. Eur J Biochem. 1985 Jul 15;150(2):265–269. [PubMed]
  • Lin T, Allen RW. Isolation and characterization of a 37,000-dalton protein associated with the erythrocyte membrane. J Biol Chem. 1986 Apr 5;261(10):4594–4599. [PubMed]
  • Allen RW, Trach KA, Hoch JA. Identification of the 37-kDa protein displaying a variable interaction with the erythroid cell membrane as glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 1987 Jan 15;262(2):649–653. [PubMed]
  • Caswell AH, Corbett AM. Interaction of glyceraldehyde-3-phosphate dehydrogenase with isolated microsomal subfractions of skeletal muscle. J Biol Chem. 1985 Jun 10;260(11):6892–6898. [PubMed]
  • Kawamoto RM, Caswell AH. Autophosphorylation of glyceraldehydephosphate dehydrogenase and phosphorylation of protein from skeletal muscle microsomes. Biochemistry. 1986 Feb 11;25(3):657–661. [PubMed]
  • Perucho M, Salas J, Salas ML. Identification of the mammalian DNA-binding protein P8 as glyceraldehyde-3-phosphate dehydrogenase. Eur J Biochem. 1977 Dec;81(3):557–562. [PubMed]
  • Morgenegg G, Winkler GC, Hübscher U, Heizmann CW, Mous J, Kuenzle CC. Glyceraldehyde-3-phosphate dehydrogenase is a nonhistone protein and a possible activator of transcription in neurons. J Neurochem. 1986 Jul;47(1):54–62. [PubMed]
  • Stancel GM, Deal WC., Jr Reversible dissociation of yeast glyceraldehyde 3-phosphate dehydrogenase by adenosine triphosphate. Biochemistry. 1969 Oct;8(10):4005–4011. [PubMed]
  • Ovãdi J, Telegdi M, Batke J, Keleti T. Functional non-identity of subunits and isolation of active dimers of D-glyceraldehyde-3-phosphate dehydrogenase. Eur J Biochem. 1971 Oct 14;22(3):430–438. [PubMed]
  • Williams KR, Reddigari S, Patel GL. Identification of a nucleic acid helix-destabilizing protein from rat liver as lactate dehydrogenase-5. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5260–5264. [PMC free article] [PubMed]
  • Duester G, Jörnvall H, Hatfield GW. Intron-dependent evolution of the nucleotide-binding domains within alcohol dehydrogenase and related enzymes. Nucleic Acids Res. 1986 Mar 11;14(5):1931–1941. [PMC free article] [PubMed]
  • Gupta PK, Sirover MA. Altered temporal expression of DNA repair in hypermutable Bloom's syndrome cells. Proc Natl Acad Sci U S A. 1984 Feb;81(3):757–761. [PMC free article] [PubMed]
  • Dehazya P, Sirover MA. Regulation of hypoxanthine DNA glycosylase in normal human and Bloom's syndrome fibroblasts. Cancer Res. 1986 Aug;46(8):3756–3761. [PubMed]
  • Kim S, Vollberg TM, Ro JY, Kim M, Sirover MA. O6-methylguanine methyltransferase increases before S phase in normal human cells but does not increase in hypermutable Bloom's syndrome cells. Mutat Res. 1986 Feb;173(2):141–145. [PubMed]
  • Willis AE, Lindahl T. DNA ligase I deficiency in Bloom's syndrome. Nature. 1987 Jan 22;325(6102):355–357. [PubMed]
  • Chan JY, Becker FF, German J, Ray JH. Altered DNA ligase I activity in Bloom's syndrome cells. Nature. 1987 Jan 22;325(6102):357–359. [PubMed]
  • Mezzina M, Nardelli J, Nocentini S, Remault G, Sarasin A. DNA ligase activity in human cell lines from normal donors and Bloom's syndrome patients. Nucleic Acids Res. 1989 Apr 25;17(8):3091–3106. [PMC free article] [PubMed]
  • Kenne K, Ljungquist S. Expression of a DNA-ligase-stimulatory factor in Bloom's syndrome cell line GM1492. Eur J Biochem. 1988 Jun 15;174(3):465–470. [PubMed]
  • Vollberg TM, Seal G, Sirover MA. Monoclonal antibodies detect conformational abnormality of uracil DNA glycosylase in Bloom's syndrome cells. Carcinogenesis. 1987 Nov;8(11):1725–1729. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...