Because of its structure and variable base composition, DNA is not an isotropic material. The overall objective of this work is to understand how the local properties of DNA depend on its sequence. DNA in cells is folded into higher order structures, whose energetics depend on the local shape and resistance to deformation. Most of the human genome does not code for proteins, but may contain signals for folding and regulatory regions if we could read them. Understanding the variation of DNA flexibility and curvature with sequence should help provide the needed decoding algorithm. The method of DNA cyclization kinetics, using specially designed cyclization constructs in a high-throughput mode, will be used to characterize the properties of specific sequence elements, alone and in complex with ligands such as proteins and sequence- specific polyamides. The sequence-dependence of the dynamic properties of DNA deformation is also poorly understood at present, a deficit that the proposed work will address through the kinetic and dynamic properties of protein and polyamide complexes, with a special focus on cases in which the DNA is bent.
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| Huang, Shar-yin N; Crothers, Donald M (2008) The role of nucleotide cofactor binding in cooperativity and specificity of MutS recognition. J Mol Biol 384:31-47 |
| Kuznetsov, Serguei V; Sugimura, Sawako; Vivas, Paula et al. (2006) Direct observation of DNA bending/unbending kinetics in complex with DNA-bending protein IHF. Proc Natl Acad Sci U S A 103:18515-20 |
| Sugimura, Sawako; Crothers, Donald M (2006) Stepwise binding and bending of DNA by Escherichia coli integration host factor. Proc Natl Acad Sci U S A 103:18510-4 |
| Zhang, Yongli; McEwen, Abbye E; Crothers, Donald M et al. (2006) Statistical-mechanical theory of DNA looping. Biophys J 90:1903-12 |
| Wickiser, J Kenneth; Winkler, Wade C; Breaker, Ronald R et al. (2005) The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Mol Cell 18:49-60 |
| Zhang, Yongli; Xi, Zhiqun; Hegde, Rashmi S et al. (2004) Predicting indirect readout effects in protein-DNA interactions. Proc Natl Acad Sci U S A 101:8337-41 |
| Bartoschek, Stefan; Buurman, Gerrit; Geierstanger, Bernhard H et al. (2003) Measurement and ab initio calculation of CSA/dipole-dipole cross-correlated relaxation provide insight into the mechanism of a H2-forming dehydrogenase. J Am Chem Soc 125:13308-9 |
| Barbic, Andrej; Zimmer, Daniel P; Crothers, Donald M (2003) Structural origins of adenine-tract bending. Proc Natl Acad Sci U S A 100:2369-73 |
| Zhang, Yongli; Crothers, Donald M (2003) Statistical mechanics of sequence-dependent circular DNA and its application for DNA cyclization. Biophys J 84:136-53 |
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