This proposal is the second five-year competitive renewal request to continue our ongoing program project studies of DNA structure, dynamics and recognition for the period 1994-98. The solution structure of a variety of biologically important sequences (synthesized in the Core lab) will be studied by chemical probe methods and by high-resolution NRM distance geometry methods. In parallel studies the sequence-dependent dynamics of DNA will be investigated on various timescales via a variety f spectroscopic relaxation techniques, including solid-state NMR, solution-state NMR, EPR (pulsed ELDOR and CW methods) and laser optical (FPA & DLS) methods. Structural measurements using isotopically labelled DNA (synthesized by the Core lab) will also be carried out using solid-state methods (REDOR/DRAMA). The structure of zinc-finger proteins that recognize specific DNA sequences will be determined by high-resolution NMR. Finally, the Core lab will supervise and coordinate the construction of a new 750 MHz NMR spectrometer to increase the sensitivity and resolution of ongoing NMR studies, as well as continuing its role as a DNA synthesis facility by providing normal and isotopically labelled nucleic acid sequences to the participating research groups.
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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 |
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| 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 |
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