Research is proposed in four interrelated areas: (1) Photochemical detection of linear dichroism will be used to determine the orientation and helical periodicities of specific regions of DNA in chromatin fibers and other DNA-containing organelles. The experiment utilizes a polarized laser pulse applied to samples oriented in an electric field, and the local dichroism is detected by DNA chain cleavage or photochemical attachment of a radiolabelled psoralen. (2) The macromolecular motional dynamics of linear and systematically bent DNA fragments and large DNA molecules in solution and electrophoresis gels will be characterized using the observed time-dependence of the response of the optical anisotropy to pulsed electric fields and flash bleaching. The objectives include analysis by hydrodynamic theory of the extent of bending of kinetoplast DNA fragments, and a study of the mechanism of electrophoretic transport through gels. (3) The dynamics of E. coli lac repressor translocation by direct transfer and sliding will be studied using fast kinetic mixing and flash techniques, along with gel electrophoretic analysis of reaction products. (4) Double helical DNA oligonucleotides containing bulge defects will be synthesized, and their stability compared to the corresponding perfect helix to determine the probability of bulge defect formation in DNA. T-jump methods will be used, and the interaction of frameshift mutagens with bulge defects will be examined by equilibrium and relaxation kinetic methods. The proposed experiments share many features of methodology and materials used, and have a common focus on exploiting and studying the time-dependent properties of DNA and its complexes.
| Xi, Zhiqun; Zhang, Yongli; Hegde, Rashmi S et al. (2010) Anomalous DNA binding by E2 regulatory protein driven by spacer sequence TATA. Nucleic Acids Res 38:3827-33 |
| 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 |
| Zhang, Yongli; McEwen, Abbye E; Crothers, Donald M et al. (2006) Statistical-mechanical theory of DNA looping. Biophys J 90:1903-12 |
| 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 |
| 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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