In this Program Project renewal application, we will continue to investigate the structural and dynamic aspects of DNA as they relate to biological recognition. The Core Facility will continue to provide members of the Project with DNA samples (including isotopically labelled DNA) and to maintain a state-of- the-art NMR and data processing facility. The variation of DNA structure as a function of sequence will be studied in several biologically important DNA sequences by a variety of techniques, including distance geometry methods. The sequences to be studied include restriction endonuclease sites, promoters, enhancer sites, and operator DNAs. The dynamic behavior of DNA will be studied across several timescales using high-resolution NMR, solid-state deuterium NMR, ESR and optical relaxation methods. Sequence-specific complexes of DNA with drugs and repressor proteins will be studied by optical methods and by high- resolution NMR methods, including heteronuclear NMR.
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| Edfeldt, N B Fredrik; Harwood, Eric A; Sigurdsson, Snorri Th et al. (2004) Solution structure of a nitrous acid induced DNA interstrand cross-link. Nucleic Acids Res 32:2785-94 |
| Okonogi, T M; Alley, S C; Reese, A W et al. (2002) Sequence-dependent dynamics of duplex DNA: the applicability of a dinucleotide model. Biophys J 83:3446-59 |
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| Meints, G A; Karlsson, T; Drobny, G P (2001) Modeling furanose ring dynamics in DNA. J Am Chem Soc 123:10030-8 |
| Meints, G A; Drobny, G P (2001) Dynamic impact of methylation at the M. Hhai target site: a solid-state deuterium NMR study. Biochemistry 40:12436-43 |
| Okonogi, T M; Alley, S C; Reese, A W et al. (2000) Sequence-dependent dynamics in duplex DNA. Biophys J 78:2560-71 |
| Harwood, E A; Hopkins, P B; Sigurdsson, S T (2000) Chemical synthesis of cross-link lesions found in nitrous acid treated DNA: a general method for the preparation of N2-substituted 2'-deoxyguanosines. J Org Chem 65:2959-64 |
| Geahigan, K B; Meints, G A; Hatcher, M E et al. (2000) The dynamic impact of CpG methylation in DNA. Biochemistry 39:4939-46 |
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