Abstract
The gene encoding DNA ligase I, the major DNA ligase activity in proliferating mammalian cells, maps to human chromosome 19q13.2-13.3. We have determined the complete structure of the gene, which is composed of 28 exons spanning 53kb on this chromosome. The first exon is untranslated, and utilises a GC dinucleotide instead of the canonical GT splice donor. The 5' flanking region lacks a TATA box and is highly GC-rich, as is characteristic of a 'housekeeping' gene. In common with the promoters of genes encoding other DNA replication enzymes, such as DNA polymerase alpha, the 5' flanking region of the DNA ligase I gene contains recognition elements for several transcription factors which may mediate increased expression in quiescent cells in response to growth factors.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alder H., Yoshinouchi M., Prystowsky M. B., Appasamy P., Baserga R. A conserved region in intron 1 negatively regulates the expression of the PCNA gene. Nucleic Acids Res. 1992 Apr 11;20(7):1769–1775. doi: 10.1093/nar/20.7.1769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aoufouchi S., Hardy S., Prigent C., Philippe M., Thiebaud P. Reinvestigation of DNA ligase I in axolotl and Pleurodeles development. Nucleic Acids Res. 1991 Aug 25;19(16):4395–4398. doi: 10.1093/nar/19.16.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aslanidis C., Jansen G., Amemiya C., Shutler G., Mahadevan M., Tsilfidis C., Chen C., Alleman J., Wormskamp N. G., Vooijs M. Cloning of the essential myotonic dystrophy region and mapping of the putative defect. Nature. 1992 Feb 6;355(6360):548–551. doi: 10.1038/355548a0. [DOI] [PubMed] [Google Scholar]
- Avvedimento V. E., Vogeli G., Yamada Y., Maizel J. V., Jr, Pastan I., de Crombrugghe B. Correlation between splicing sites within an intron and their sequence complementarity with U1 RNA. Cell. 1980 Oct;21(3):689–696. doi: 10.1016/0092-8674(80)90432-8. [DOI] [PubMed] [Google Scholar]
- Barker D. G., White J. H., Johnston L. H. Molecular characterisation of the DNA ligase gene, CDC17, from the fission yeast Schizosaccharomyces pombe. Eur J Biochem. 1987 Feb 2;162(3):659–667. doi: 10.1111/j.1432-1033.1987.tb10688.x. [DOI] [PubMed] [Google Scholar]
- Barker D. G., White J. H., Johnston L. H. The nucleotide sequence of the DNA ligase gene (CDC9) from Saccharomyces cerevisiae: a gene which is cell-cycle regulated and induced in response to DNA damage. Nucleic Acids Res. 1985 Dec 9;13(23):8323–8337. doi: 10.1093/nar/13.23.8323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barnes D. E., Johnston L. H., Kodama K., Tomkinson A. E., Lasko D. D., Lindahl T. Human DNA ligase I cDNA: cloning and functional expression in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6679–6683. doi: 10.1073/pnas.87.17.6679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barnes D. E., Kodama K., Tynan K., Trask B. J., Christensen M., De Jong P. J., Spurr N. K., Lindahl T., Mohrenweiser H. W. Assignment of the gene encoding DNA ligase I to human chromosome 19q13.2-13.3. Genomics. 1992 Jan;12(1):164–166. doi: 10.1016/0888-7543(92)90422-o. [DOI] [PubMed] [Google Scholar]
- Barnes D. E., Tomkinson A. E., Lehmann A. R., Webster A. D., Lindahl T. Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents. Cell. 1992 May 1;69(3):495–503. doi: 10.1016/0092-8674(92)90450-q. [DOI] [PubMed] [Google Scholar]
- Biggin M., Farrell P. J., Barrell B. G. Transcription and DNA sequence of the BamHI L fragment of B95-8 Epstein-Barr virus. EMBO J. 1984 May;3(5):1083–1090. doi: 10.1002/j.1460-2075.1984.tb01933.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bird A., Taggart M., Frommer M., Miller O. J., Macleod D. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell. 1985 Jan;40(1):91–99. doi: 10.1016/0092-8674(85)90312-5. [DOI] [PubMed] [Google Scholar]
- Broderick T. P., Schaff D. A., Bertino A. M., Dush M. K., Tischfield J. A., Stambrook P. J. Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement. Proc Natl Acad Sci U S A. 1987 May;84(10):3349–3353. doi: 10.1073/pnas.84.10.3349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
- Elder R. H., Rossignol J. M. DNA ligases from rat liver. Purification and partial characterization of two molecular forms. Biochemistry. 1990 Jun 26;29(25):6009–6017. doi: 10.1021/bi00477a019. [DOI] [PubMed] [Google Scholar]
- Farrell P. J., Deininger P. L., Bankier A., Barrell B. Homologous upstream sequences near Epstein-Barr virus promoters. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1565–1569. doi: 10.1073/pnas.80.6.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flemington E., Bradshaw H. D., Jr, Traina-Dorge V., Slagel V., Deininger P. L. Sequence, structure and promoter characterization of the human thymidine kinase gene. Gene. 1987;52(2-3):267–277. doi: 10.1016/0378-1119(87)90053-9. [DOI] [PubMed] [Google Scholar]
- Hawkins J. D. A survey on intron and exon lengths. Nucleic Acids Res. 1988 Nov 11;16(21):9893–9908. doi: 10.1093/nar/16.21.9893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kauffman M. G., Kelly T. J. Cell cycle regulation of thymidine kinase: residues near the carboxyl terminus are essential for the specific degradation of the enzyme at mitosis. Mol Cell Biol. 1991 May;11(5):2538–2546. doi: 10.1128/mcb.11.5.2538. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knight G. B., Gudas J. M., Pardee A. B. Cell-cycle-specific interaction of nuclear DNA-binding proteins with a CCAAT sequence from the human thymidine kinase gene. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8350–8354. doi: 10.1073/pnas.84.23.8350. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kodama K., Barnes D. E., Lindahl T. In vitro mutagenesis and functional expression in Escherichia coli of a cDNA encoding the catalytic domain of human DNA ligase I. Nucleic Acids Res. 1991 Nov 25;19(22):6093–6099. doi: 10.1093/nar/19.22.6093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lasko D. D., Tomkinson A. E., Lindahl T. Mammalian DNA ligases. Biosynthesis and intracellular localization of DNA ligase I. J Biol Chem. 1990 Jul 25;265(21):12618–12622. [PubMed] [Google Scholar]
- Lee K. A., Hai T. Y., SivaRaman L., Thimmappaya B., Hurst H. C., Jones N. C., Green M. R. A cellular protein, activating transcription factor, activates transcription of multiple E1A-inducible adenovirus early promoters. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8355–8359. doi: 10.1073/pnas.84.23.8355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lindahl T., Barnes D. E. Mammalian DNA ligases. Annu Rev Biochem. 1992;61:251–281. doi: 10.1146/annurev.bi.61.070192.001343. [DOI] [PubMed] [Google Scholar]
- Lowndes N. F., Johnson A. L., Johnston L. H. Coordination of expression of DNA synthesis genes in budding yeast by a cell-cycle regulated trans factor. Nature. 1991 Mar 21;350(6315):247–250. doi: 10.1038/350247a0. [DOI] [PubMed] [Google Scholar]
- Martin-Gallardo A., McCombie W. R., Gocayne J. D., FitzGerald M. G., Wallace S., Lee B. M., Lamerdin J., Trapp S., Kelley J. M., Liu L. I. Automated DNA sequencing and analysis of 106 kilobases from human chromosome 19q13.3. Nat Genet. 1992 Apr;1(1):34–39. doi: 10.1038/ng0492-34. [DOI] [PubMed] [Google Scholar]
- Mezzina M., Nocentini S. DNA ligase activity in UV-irradiated monkey kidney cells. Nucleic Acids Res. 1978 Nov;5(11):4317–4328. doi: 10.1093/nar/5.11.4317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray V. Improved double-stranded DNA sequencing using the linear polymerase chain reaction. Nucleic Acids Res. 1989 Nov 11;17(21):8889–8889. doi: 10.1093/nar/17.21.8889. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [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]
- Pearson B. E., Nasheuer H. P., Wang T. S. Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells. Mol Cell Biol. 1991 Apr;11(4):2081–2095. doi: 10.1128/mcb.11.4.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Petrini J. H., Huwiler K. G., Weaver D. T. A wild-type DNA ligase I gene is expressed in Bloom's syndrome cells. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7615–7619. doi: 10.1073/pnas.88.17.7615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Prigent C., Lasko D. D., Kodama K., Woodgett J. R., Lindahl T. Activation of mammalian DNA ligase I through phosphorylation by casein kinase II. EMBO J. 1992 Aug;11(8):2925–2933. doi: 10.1002/j.1460-2075.1992.tb05362.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [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]
- Söderhäll S. DNA ligases during rat liver regeneration. Nature. 1976 Apr 15;260(5552):640–642. doi: 10.1038/260640a0. [DOI] [PubMed] [Google Scholar]
- Teraoka H., Tsukada K. Eukaryotic DNA ligase. Purification and properties of the enzyme from bovine thymus, and immunochemical studies of the enzyme from animal tissues. J Biol Chem. 1982 May 10;257(9):4758–4763. [PubMed] [Google Scholar]
- Tomkinson A. E., Lasko D. D., Daly G., Lindahl T. Mammalian DNA ligases. Catalytic domain and size of DNA ligase I. J Biol Chem. 1990 Jul 25;265(21):12611–12617. [PubMed] [Google Scholar]
- Tomkinson A. E., Roberts E., Daly G., Totty N. F., Lindahl T. Three distinct DNA ligases in mammalian cells. J Biol Chem. 1991 Nov 15;266(32):21728–21735. [PubMed] [Google Scholar]
- Tomkinson A. E., Totty N. F., Ginsburg M., Lindahl T. Location of the active site for enzyme-adenylate formation in DNA ligases. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):400–404. doi: 10.1073/pnas.88.2.400. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Traut T. W. Do exons code for structural or functional units in proteins? Proc Natl Acad Sci U S A. 1988 May;85(9):2944–2948. doi: 10.1073/pnas.85.9.2944. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Travali S., Ku D. H., Rizzo M. G., Ottavio L., Baserga R., Calabretta B. Structure of the human gene for the proliferating cell nuclear antigen. J Biol Chem. 1989 May 5;264(13):7466–7472. [PubMed] [Google Scholar]
- Tynan K., Olsen A., Trask B., de Jong P., Thompson J., Zimmermann W., Carrano A., Mohrenweiser H. Assembly and analysis of cosmid contigs in the CEA-gene family region of human chromosome 19. Nucleic Acids Res. 1992 Apr 11;20(7):1629–1636. doi: 10.1093/nar/20.7.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wahl A. F., Geis A. M., Spain B. H., Wong S. W., Korn D., Wang T. S. Gene expression of human DNA polymerase alpha during cell proliferation and the cell cycle. Mol Cell Biol. 1988 Nov;8(11):5016–5025. doi: 10.1128/mcb.8.11.5016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Webster A. D., Barnes D. E., Arlett C. F., Lehmann A. R., Lindahl T. Growth retardation and immunodeficiency in a patient with mutations in the DNA ligase I gene. Lancet. 1992 Jun 20;339(8808):1508–1509. doi: 10.1016/0140-6736(92)91266-b. [DOI] [PubMed] [Google Scholar]
- Weeda G., Ma L. B., van Ham R. C., van der Eb A. J., Hoeijmakers J. H. Structure and expression of the human XPBC/ERCC-3 gene involved in DNA repair disorders xeroderma pigmentosum and Cockayne's syndrome. Nucleic Acids Res. 1991 Nov 25;19(22):6301–6308. doi: 10.1093/nar/19.22.6301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- White J. H., Barker D. G., Nurse P., Johnston L. H. Periodic transcription as a means of regulating gene expression during the cell cycle: contrasting modes of expression of DNA ligase genes in budding and fission yeast. EMBO J. 1986 Jul;5(7):1705–1709. doi: 10.1002/j.1460-2075.1986.tb04414.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang S. W., Chan J. Y. Analysis of the formation of AMP-DNA intermediate and the successive reaction by human DNA ligases I and II. J Biol Chem. 1992 Apr 25;267(12):8117–8122. [PubMed] [Google Scholar]
- van Duin M., Koken M. H., van den Tol J., ten Dijke P., Odijk H., Westerveld A., Bootsma D., Hoeijmakers J. H. Genomic characterization of the human DNA excision repair gene ERCC-1. Nucleic Acids Res. 1987 Nov 25;15(22):9195–9213. doi: 10.1093/nar/15.22.9195. [DOI] [PMC free article] [PubMed] [Google Scholar]