Abstract
A guanine-rich single-stranded DNA from the human immunoglobulin switch region was shown by Sen and Gilbert [Nature, (1988) 334, 364-366] to be able to self-associate to form a stable four-stranded parallel DNA structure. Topoisomerase II did not cleave the single-stranded DNA molecule. Surprisingly, the enzyme did cleave the same DNA sequence when it was annealed into the four-stranded structure. The two cleavage sites observed were the same as those found when this DNA molecule was paired with a complementary molecule to create a normal B-DNA duplex. These cleavages were shown to be protein-linked and reversible by the addition of salt, suggesting a normal topoisomerase II reaction mechanism. In addition, an eight-stranded DNA molecule created by the association of a complementary oligonucleotide with the four-stranded structure was also cleaved by topoisomerase II despite being resistant to restriction endonuclease digestion. These results suggest that a single strand of DNA may possess the sequence information to direct topoisomerase II to a binding site, but the site must be base paired in a proper manner to do so. This demonstration of the ability of a four-stranded DNA molecule to be a substrate for an enzyme further suggests that these DNA structures may be present in cells.
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Selected References
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- Berrios M., Osheroff N., Fisher P. A. In situ localization of DNA topoisomerase II, a major polypeptide component of the Drosophila nuclear matrix fraction. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4142–4146. doi: 10.1073/pnas.82.12.4142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carcamo J., Maldonado E., Cortes P., Ahn M. H., Ha I., Kasai Y., Flint J., Reinberg D. A TATA-like sequence located downstream of the transcription initiation site is required for expression of an RNA polymerase II transcribed gene. Genes Dev. 1990 Sep;4(9):1611–1622. doi: 10.1101/gad.4.9.1611. [DOI] [PubMed] [Google Scholar]
- Chung I. K., Muller M. T. Aggregates of oligo(dG) bind and inhibit topoisomerase II activity and induce formation of large networks. J Biol Chem. 1991 May 25;266(15):9508–9514. [PubMed] [Google Scholar]
- DiNardo S., Voelkel K., Sternglanz R. DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc Natl Acad Sci U S A. 1984 May;81(9):2616–2620. doi: 10.1073/pnas.81.9.2616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Earnshaw W. C., Halligan B., Cooke C. A., Heck M. M., Liu L. F. Topoisomerase II is a structural component of mitotic chromosome scaffolds. J Cell Biol. 1985 May;100(5):1706–1715. doi: 10.1083/jcb.100.5.1706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gale K. C., Osheroff N. Uncoupling the DNA cleavage and religation activities of topoisomerase II with a single-stranded nucleic acid substrate: evidence for an active enzyme-cleaved DNA intermediate. Biochemistry. 1990 Oct 16;29(41):9538–9545. doi: 10.1021/bi00493a007. [DOI] [PubMed] [Google Scholar]
- Gasser S. M., Laemmli U. K. Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster. Cell. 1986 Aug 15;46(4):521–530. doi: 10.1016/0092-8674(86)90877-9. [DOI] [PubMed] [Google Scholar]
- Holm C., Goto T., Wang J. C., Botstein D. DNA topoisomerase II is required at the time of mitosis in yeast. Cell. 1985 Jun;41(2):553–563. doi: 10.1016/s0092-8674(85)80028-3. [DOI] [PubMed] [Google Scholar]
- Ikeda H. Bacteriophage T4 DNA topoisomerase mediates illegitimate recombination in vitro. Proc Natl Acad Sci U S A. 1986 Feb;83(4):922–926. doi: 10.1073/pnas.83.4.922. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kreuzer K. N. Recognition of single-stranded DNA by the bacteriophage T4-induced type II topoisomerase. J Biol Chem. 1984 Apr 25;259(8):5347–5354. [PubMed] [Google Scholar]
- Liu L. F., Wang J. C. Supercoiling of the DNA template during transcription. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7024–7027. doi: 10.1073/pnas.84.20.7024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miura-Masuda A., Ikeda H. The DNA gyrase of Escherichia coli participates in the formation of a spontaneous deletion by recA-independent recombination in vivo. Mol Gen Genet. 1990 Feb;220(3):345–352. doi: 10.1007/BF00391737. [DOI] [PubMed] [Google Scholar]
- Muller M. T., Mehta V. B. DNase I hypersensitivity is independent of endogenous topoisomerase II activity during chicken erythrocyte differentiation. Mol Cell Biol. 1988 Sep;8(9):3661–3669. doi: 10.1128/mcb.8.9.3661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muller M. T., Pfund W. P., Mehta V. B., Trask D. K. Eukaryotic type I topoisomerase is enriched in the nucleolus and catalytically active on ribosomal DNA. EMBO J. 1985 May;4(5):1237–1243. doi: 10.1002/j.1460-2075.1985.tb03766.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muller M. T., Spitzner J. R., DiDonato J. A., Mehta V. B., Tsutsui K., Tsutsui K. Single-strand DNA cleavages by eukaryotic topoisomerase II. Biochemistry. 1988 Nov 1;27(22):8369–8379. doi: 10.1021/bi00422a012. [DOI] [PubMed] [Google Scholar]
- Osheroff N., Zechiedrich E. L. Calcium-promoted DNA cleavage by eukaryotic topoisomerase II: trapping the covalent enzyme-DNA complex in an active form. Biochemistry. 1987 Jul 14;26(14):4303–4309. doi: 10.1021/bi00388a018. [DOI] [PubMed] [Google Scholar]
- Rose D., Thomas W., Holm C. Segregation of recombined chromosomes in meiosis I requires DNA topoisomerase II. Cell. 1990 Mar 23;60(6):1009–1017. doi: 10.1016/0092-8674(90)90349-j. [DOI] [PubMed] [Google Scholar]
- Sen D., Gilbert W. A sodium-potassium switch in the formation of four-stranded G4-DNA. Nature. 1990 Mar 29;344(6265):410–414. doi: 10.1038/344410a0. [DOI] [PubMed] [Google Scholar]
- Sen D., Gilbert W. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 1988 Jul 28;334(6180):364–366. doi: 10.1038/334364a0. [DOI] [PubMed] [Google Scholar]
- Snapka R. M., Powelson M. A., Strayer J. M. Swiveling and decatenation of replicating simian virus 40 genomes in vivo. Mol Cell Biol. 1988 Feb;8(2):515–521. doi: 10.1128/mcb.8.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spitzner J. R., Chung I. K., Muller M. T. Eukaryotic topoisomerase II preferentially cleaves alternating purine-pyrimidine repeats. Nucleic Acids Res. 1990 Jan 11;18(1):1–11. doi: 10.1093/nar/18.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spitzner J. R., Muller M. T. A consensus sequence for cleavage by vertebrate DNA topoisomerase II. Nucleic Acids Res. 1988 Jun 24;16(12):5533–5556. doi: 10.1093/nar/16.12.5533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spitzner J. R., Muller M. T. Application of a degenerate consensus sequence to quantify recognition sites by vertebrate DNA topoisomerase II. J Mol Recognit. 1989 Sep;2(2):63–74. doi: 10.1002/jmr.300020204. [DOI] [PubMed] [Google Scholar]
- Sundquist W. I., Klug A. Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops. Nature. 1989 Dec 14;342(6251):825–829. doi: 10.1038/342825a0. [DOI] [PubMed] [Google Scholar]
- Trask D. K., Muller M. T. Biochemical characterization of topoisomerase I purified from avian erythrocytes. Nucleic Acids Res. 1983 May 11;11(9):2779–2800. doi: 10.1093/nar/11.9.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uemura T., Yanagida M. Isolation of type I and II DNA topoisomerase mutants from fission yeast: single and double mutants show different phenotypes in cell growth and chromatin organization. EMBO J. 1984 Aug;3(8):1737–1744. doi: 10.1002/j.1460-2075.1984.tb02040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang J. C., Caron P. R., Kim R. A. The role of DNA topoisomerases in recombination and genome stability: a double-edged sword? Cell. 1990 Aug 10;62(3):403–406. doi: 10.1016/0092-8674(90)90002-v. [DOI] [PubMed] [Google Scholar]
- Weinreb A., Collier D. A., Birshtein B. K., Wells R. D. Left-handed Z-DNA and intramolecular triplex formation at the site of an unequal sister chromatid exchange. J Biol Chem. 1990 Jan 25;265(3):1352–1359. [PubMed] [Google Scholar]
- Williamson J. R., Raghuraman M. K., Cech T. R. Monovalent cation-induced structure of telomeric DNA: the G-quartet model. Cell. 1989 Dec 1;59(5):871–880. doi: 10.1016/0092-8674(89)90610-7. [DOI] [PubMed] [Google Scholar]
- Yang G. C., Kunze N., Baumgärtner B., Jiang Z. Y., Sapp M., Knippers R., Richter A. Molecular structures of two human DNA topoisomerase I retrosequences. Gene. 1990 Jul 16;91(2):247–253. doi: 10.1016/0378-1119(90)90095-9. [DOI] [PubMed] [Google Scholar]