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Difference Topology: Analysis of High-Order DNA-Protin Assemblies

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Part of the book series: The IMA Volumes in Mathematics and its Applications ((IMA,volume 150))

Abstract

DNA transactions in biological systems are often carried out by multisubunit protein assemblies that confer a defined topology on their DNA target sites. A subset of biochemically characterized site-specific recombination reactions and at least one DNA transposition reaction have been subject to extensive topological analysis. It is conceivable that interactions between the replication apparatus and origins of replication or those between transcription machineries and promoters, enhancers and repressor binding sequences also impose precise topological constraints on the path of DNA. Such ‘topological filters’ are thought to stabilize DNA-protein configurations that are conducive to triggering the chemical steps of the respective reactions. ‘Difference topology’ is a simple method for deciphering the DNA topology within complex DNA-protein machines that are not readily amenable to standard structural analyses. The logic is to trap the crossings formed by distinct DNA segments by tying them into knots or links by site-specific DNA inversion and deletion, respectively, carried out by a recombinase. The number of such crossings can then be counted by analytical methods such as gel electrophoresis or electron microscopy.

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References

  1. Chaconas G. and Harshey R.M., Transposition of phage Mu DNA. In Mobile DNA II, Eds. Craig. N.L., Craigie R., Gellert M., and Lambowitz A.M. (Washington DC: ASM Press). pp. 384–402, 2002.

    Google Scholar 

  2. Chen Y., Narendra U., Iype L.E., Cox M.M., and Rice P.A., Crystal structure of a Flp recombinase-Holliday junction complex: assembly of an active oligomer by helix swapping. Mol. Cell. 6: 885–897, 2000.

    CAS  PubMed  Google Scholar 

  3. Cozzarelli N.R., UCLA Symp Mol. Cell. Biol. 47: 1, 1986.

    Google Scholar 

  4. Cozzarelli N.R., Krasnow M.A., Gerrard S.P., and White J.H., A topological treatment of recombination and topoisomerases. Cold Spring Harb. Symp. Quant. Biol. 49: 383–400, 1984.

    Article  CAS  Google Scholar 

  5. Cozzarelli N.R., Krasnow M.A., Gerrard S.P., and White J., Primer on the topology and geometry of DNA supercoiling: In DNA topology and its biological effects. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1990.

    Google Scholar 

  6. Dhar G., Sanders E.R., and Johnson R.C., Architecture of the Hin synaptic complex during recombination: the recombinase subunits translocate with the DNA strands. Cell. 119: 33–45, 2004.

    Article  CAS  Google Scholar 

  7. Grainge I., Buck D., and Jayaram M., Geometry of site alignment during int family recombination: antiparallel synapsis by the Flp recombinase. J. Mol. Biol. 298: 749–764, 2000.

    Article  CAS  Google Scholar 

  8. Grainge I., Pathania S., Vologodskii A., Harshey R.M., and Jayaram M., Symmetric DNA sites are functionally asymmetric within Flp and Cre site-specific DNA recombination synapses. J. Mol. Biol. 320: 515–527, 2000.

    Article  Google Scholar 

  9. Grindley N.D., The movement of Tn3 like elements: Transposition and cointegrate resolution. In Mobile DNA II, Eds. Craig N.L., Craigie R., Gellert M., and Lambowitz A.M. (Washington DC: ASM Press). pp. 272–302, 2002.

    Google Scholar 

  10. Grindley N.D., Whiteson K.L., and Rice P.A., Mechanisms of site-specific recombination. Annu. Rev. Biochem. 75: 567–605, 2006.

    Article  CAS  Google Scholar 

  11. Guo F., Gopaul D.N., and van Duyne G.D., Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse. Nature 389: 40–46, 1997.

    Article  CAS  Google Scholar 

  12. Harshey R.M. and Jayaram M., The Mu transpososome through a topological lens. Crit. Rev. Biochem. Mol. Biol. 41: 387–405, 2006.

    Article  CAS  Google Scholar 

  13. Jayaram M., Tribble G., and Grainge I., Site-specific recombination by the Flp protein of Saccharomyces cerevisiae. In Mobile DNA II, Eds. Craig N.L., Craigie R., Gellert M., and Lambowitz A.M. (Washington DC: ASM Press). pp. 192–218, 2002.

    Google Scholar 

  14. Johnson R., Bacterial site-specific DNA inversion systems. In Mobile DNA II, Eds. Craig N.L., Craigie R., Gellert M., and Lambowitz A.M. (Washington DC: ASM Press). pp. 230–271, 2002.

    Google Scholar 

  15. Kamtekar S., Ho R.S., Cocco M.J., Li W., Wenwieser S.V., Boocock M.R., Grindley N.D., and Steitz T.A., Implications of structures of synaptic tetramers of γδ resolvase for the mechanism of recombination. Proc. Natl. Acad. Sci. USA 103: 10642–10647, 2006.

    Article  CAS  Google Scholar 

  16. Kanaar R., Klippel A., Shekhtman E., Dungan J.M., Kahmann R., and Cozzarelli N.R., Processive recombination by the phage Mu Gin system: Implications for the mechanisms of DNA strand exchange, DNA site alignment, and enhancer action. Cell 62: 353–366, 1990.

    Article  CAS  Google Scholar 

  17. Kilbride E., Boocock M.R., and Stark W.M., Topological selectivity of a hybrid site-specific recombination system with elements from Tn3 res/resolvase and bacteriophage P1 loxP/Cre. J. Mol. Biol. 289: 1219–1230, 1999.

    Article  CAS  Google Scholar 

  18. Li W., Kamtekar S., Xiong Y., Sarkis G.J., Grindley N.D., and Steitz T.A., Structure of a synaptic γδ resolvase tetramer covalently linked to two cleaved DNAs. Science 309: 1210–1215, 2005.

    Article  CAS  Google Scholar 

  19. Pathania S., Jayaram M., and Harshey R.M., Path of DNA within the Mu transpososome. Transposase interactions bridging two Mu ends and the enhancer trap five DNA supercoils. Cell 109: 425–436, 2002.

    Article  CAS  Google Scholar 

  20. Pathania S., Jayaram M., and Harshey R.M., A unique right end-enhancer complex precedes synapsis of Mu ends: the enhancer is sequestered within the transpososome throughout transposition. EMBO J. 22: 3725–3736, 2003.

    Article  CAS  Google Scholar 

  21. Stahl F.W., Symposium on DNA replication and recombination. Summary. Cold Spring Harb. Symp. Quant. Biol. 43(2): 1353–1356, 1979.

    Article  Google Scholar 

  22. Sumners D.W., Ernst C., Spengler S.J., and Cozzarelli N.R., Analysis of the mechanism of DNA recombination using tangles. Q. Rev. Biophys. 28: 253–313, 1995.

    Article  CAS  Google Scholar 

  23. van Duyne G.D., A structural view of tyrosine recombinase site-specific recombination, In Mobile DNA II, Eds. Craig N.L., Craigie R., Gellert M., and Lambowitz A.M. (Washington DC: ASM Press). pp. 93–117, 2002.

    Google Scholar 

  24. Wasserman S.A. and Cozzarelli N.R., Biochemical topology: Applications to DNA recombination and replication. Science 232: 951–960, 1986.

    Article  CAS  Google Scholar 

  25. Watson M.A. and Chaconas G., Three-site synapsis during Mu DNA transposition: a critical intermediate preceding engagement of the active site. Cell 85: 435–445, 1996.

    Article  CAS  Google Scholar 

  26. Yin Z., Suzuki A., Lou Z., Jayaram M., and Harshey R.M., Interactions of phage Mu enhancer and termini that specify the assembly of a topologically unique interwrapped transpososome. J. Mol. Biol. 372: 382–396, 2007.

    Article  CAS  Google Scholar 

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Correspondence to Makkuni Jayaram .

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Jayaram, M., Harshey, R. (2009). Difference Topology: Analysis of High-Order DNA-Protin Assemblies. In: Benham, C., Harvey, S., Olson, W., Sumners, D., Swigon, D. (eds) Mathematics of DNA Structure, Function and Interactions. The IMA Volumes in Mathematics and its Applications, vol 150. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0670-0_7

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