Abstract
We recently reported the presence of four genes lying between the human alpha-globin gene cluster and the telomere of the short arm of chromosome 16 (16p). We now report that one of these genes encodes 3-methyladenine DNA glycosylase, an enzyme important in the repair of DNA after damage by alkylating agents. The gene comprises five exons, representation of which differs in independently isolated cDNA clones. Although the gene is widely expressed, the abundance of its mRNA is considerably higher in a colon adenocarcinoma cell line (HT29) than in other cell lines that were tested. The major positive erythroid-specific regulatory element controlling alpha-globin gene expression lies equidistant between the promoters of the alpha-globin genes and the 3-methyladenine DNA glycosylase gene. Interestingly, in contrast to the alpha-globin genes, expression of the 3-methyladenine DNA glycosylase gene is not influenced by the regulatory element in the human erythroleukemia cell line K562.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aruffo A., Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. doi: 10.1073/pnas.84.23.8573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berdal K. G., Bjørås M., Bjelland S., Seeberg E. Cloning and expression in Escherichia coli of a gene for an alkylbase DNA glycosylase from Saccharomyces cerevisiae; a homologue to the bacterial alkA gene. EMBO J. 1990 Dec;9(13):4563–4568. doi: 10.1002/j.1460-2075.1990.tb07909.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernardi G., Olofsson B., Filipski J., Zerial M., Salinas J., Cuny G., Meunier-Rotival M., Rodier F. The mosaic genome of warm-blooded vertebrates. Science. 1985 May 24;228(4702):953–958. doi: 10.1126/science.4001930. [DOI] [PubMed] [Google Scholar]
- Chakravarti D., Ibeanu G. C., Tano K., Mitra S. Cloning and expression in Escherichia coli of a human cDNA encoding the DNA repair protein N-methylpurine-DNA glycosylase. J Biol Chem. 1991 Aug 25;266(24):15710–15715. [PubMed] [Google Scholar]
- Chen J., Derfler B., Maskati A., Samson L. Cloning a eukaryotic DNA glycosylase repair gene by the suppression of a DNA repair defect in Escherichia coli. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7961–7965. doi: 10.1073/pnas.86.20.7961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen J., Derfler B., Samson L. Saccharomyces cerevisiae 3-methyladenine DNA glycosylase has homology to the AlkA glycosylase of E. coli and is induced in response to DNA alkylation damage. EMBO J. 1990 Dec;9(13):4569–4575. doi: 10.1002/j.1460-2075.1990.tb07910.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forrester W. C., Epner E., Driscoll M. C., Enver T., Brice M., Papayannopoulou T., Groudine M. A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. Genes Dev. 1990 Oct;4(10):1637–1649. doi: 10.1101/gad.4.10.1637. [DOI] [PubMed] [Google Scholar]
- Hatton C. S., Wilkie A. O., Drysdale H. C., Wood W. G., Vickers M. A., Sharpe J., Ayyub H., Pretorius I. M., Buckle V. J., Higgs D. R. Alpha-thalassemia caused by a large (62 kb) deletion upstream of the human alpha globin gene cluster. Blood. 1990 Jul 1;76(1):221–227. [PubMed] [Google Scholar]
- Helland D. E., Male R., Haukanes B. I., Olsen L., Haugan I., Kleppe K. Properties and mechanism of action of eukaryotic 3-methyladenine-DNA glycosylases. J Cell Sci Suppl. 1987;6:139–146. doi: 10.1242/jcs.1984.supplement_6.9. [DOI] [PubMed] [Google Scholar]
- Higgs D. R., Vickers M. A., Wilkie A. O., Pretorius I. M., Jarman A. P., Weatherall D. J. A review of the molecular genetics of the human alpha-globin gene cluster. Blood. 1989 Apr;73(5):1081–1104. [PubMed] [Google Scholar]
- Higgs D. R., Wood W. G., Jarman A. P., Sharpe J., Lida J., Pretorius I. M., Ayyub H. A major positive regulatory region located far upstream of the human alpha-globin gene locus. Genes Dev. 1990 Sep;4(9):1588–1601. doi: 10.1101/gad.4.9.1588. [DOI] [PubMed] [Google Scholar]
- Holmquist G. P. Role of replication time in the control of tissue-specific gene expression. Am J Hum Genet. 1987 Feb;40(2):151–173. [PMC free article] [PubMed] [Google Scholar]
- Klungland A., Fairbairn L., Watson A. J., Margison G. P., Seeberg E. Expression of the E.coli 3-methyladenine DNA glycosylase I gene in mammalian cells reduces the toxic and mutagenic effects of methylating agents. EMBO J. 1992 Dec;11(12):4439–4444. doi: 10.1002/j.1460-2075.1992.tb05544.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindahl T., Sedgwick B., Sekiguchi M., Nakabeppu Y. Regulation and expression of the adaptive response to alkylating agents. Annu Rev Biochem. 1988;57:133–157. doi: 10.1146/annurev.bi.57.070188.001025. [DOI] [PubMed] [Google Scholar]
- Lyon M. F. The William Allan memorial award address: X-chromosome inactivation and the location and expression of X-linked genes. Am J Hum Genet. 1988 Jan;42(1):8–16. [PMC free article] [PubMed] [Google Scholar]
- Mouchiroud D., D'Onofrio G., Aïssani B., Macaya G., Gautier C., Bernardi G. The distribution of genes in the human genome. Gene. 1991 Apr;100:181–187. doi: 10.1016/0378-1119(91)90364-h. [DOI] [PubMed] [Google Scholar]
- O'Connor T. R., Laval F. Isolation and structure of a cDNA expressing a mammalian 3-methyladenine-DNA glycosylase. EMBO J. 1990 Oct;9(10):3337–3342. doi: 10.1002/j.1460-2075.1990.tb07534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Connor T. R., Laval J. Human cDNA expressing a functional DNA glycosylase excising 3-methyladenine and 7-methylguanine. Biochem Biophys Res Commun. 1991 May 15;176(3):1170–1177. doi: 10.1016/0006-291x(91)90408-y. [DOI] [PubMed] [Google Scholar]
- Padgett R. A., Grabowski P. J., Konarska M. M., Seiler S., Sharp P. A. Splicing of messenger RNA precursors. Annu Rev Biochem. 1986;55:1119–1150. doi: 10.1146/annurev.bi.55.070186.005351. [DOI] [PubMed] [Google Scholar]
- Romao L., Cash F., Weiss I., Liebhaber S., Pirastu M., Galanello R., Loi A., Paglietti E., Ioannou P., Cao A. Human alpha-globin gene expression is silenced by terminal truncation of chromosome 16p beginning immediately 3' of the zeta-globin gene. Hum Genet. 1992 May;89(3):323–328. doi: 10.1007/BF00220551. [DOI] [PubMed] [Google Scholar]
- Saccone S., De Sario A., Della Valle G., Bernardi G. The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4913–4917. doi: 10.1073/pnas.89.11.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Samson L., Derfler B., Boosalis M., Call K. Cloning and characterization of a 3-methyladenine DNA glycosylase cDNA from human cells whose gene maps to chromosome 16. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9127–9131. doi: 10.1073/pnas.88.20.9127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seed B. An LFA-3 cDNA encodes a phospholipid-linked membrane protein homologous to its receptor CD2. 1987 Oct 29-Nov 4Nature. 329(6142):840–842. doi: 10.1038/329840a0. [DOI] [PubMed] [Google Scholar]
- Tazi J., Bird A. Alternative chromatin structure at CpG islands. Cell. 1990 Mar 23;60(6):909–920. doi: 10.1016/0092-8674(90)90339-g. [DOI] [PubMed] [Google Scholar]
- Vyas P., Vickers M. A., Simmons D. L., Ayyub H., Craddock C. F., Higgs D. R. Cis-acting sequences regulating expression of the human alpha-globin cluster lie within constitutively open chromatin. Cell. 1992 May 29;69(5):781–793. doi: 10.1016/0092-8674(92)90290-s. [DOI] [PubMed] [Google Scholar]
- Wallace S. S. AP endonucleases and DNA glycosylases that recognize oxidative DNA damage. Environ Mol Mutagen. 1988;12(4):431–477. doi: 10.1002/em.2860120411. [DOI] [PubMed] [Google Scholar]
- Washington W. J., Dunn W. C., Jr, Generoso W. M., Mitra S. Tissue-specific variation in repair activity for 3-methyladenine in DNA in two stocks of mice. Mutat Res. 1988 Mar-Apr;207(3-4):165–169. doi: 10.1016/0165-7992(88)90082-6. [DOI] [PubMed] [Google Scholar]
- Washington W. J., Foote R. S., Dunn W. C., Generoso W. M., Mitra S. Age-dependent modulation of tissue-specific repair activity for 3-methyladenine and O6-methylguanine in DNA in inbred mice. Mech Ageing Dev. 1989 Apr;48(1):43–52. doi: 10.1016/0047-6374(89)90024-9. [DOI] [PubMed] [Google Scholar]
- Wilkie A. O., Buckle V. J., Harris P. C., Lamb J., Barton N. J., Reeders S. T., Lindenbaum R. H., Nicholls R. D., Barrow M., Bethlenfalvay N. C. Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. I. Cases due to deletions involving chromosome band 16p13.3. Am J Hum Genet. 1990 Jun;46(6):1112–1126. [PMC free article] [PubMed] [Google Scholar]
- Wilkie A. O., Higgs D. R., Rack K. A., Buckle V. J., Spurr N. K., Fischel-Ghodsian N., Ceccherini I., Brown W. R., Harris P. C. Stable length polymorphism of up to 260 kb at the tip of the short arm of human chromosome 16. Cell. 1991 Feb 8;64(3):595–606. doi: 10.1016/0092-8674(91)90243-r. [DOI] [PubMed] [Google Scholar]
- Wilkie A. O., Lamb J., Harris P. C., Finney R. D., Higgs D. R. A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n. Nature. 1990 Aug 30;346(6287):868–871. doi: 10.1038/346868a0. [DOI] [PubMed] [Google Scholar]
- Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]