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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM032681-09
Application #
3096207
Study Section
Special Emphasis Panel (SSS (R))
Project Start
1984-01-01
Project End
1993-12-31
Budget Start
1992-01-01
Budget End
1992-12-31
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Edfeldt, N B Fredrik; Harwood, Eric A; Sigurdsson, Snorri Th et al. (2004) Sequence context effect on the structure of nitrous acid induced DNA interstrand cross-links. Nucleic Acids Res 32:2795-801
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
Okonogi, Tamara M; Alley, Stephen C; Harwood, Eric A et al. (2002) Phosphate backbone neutralization increases duplex DNA flexibility: a model for protein binding. Proc Natl Acad Sci U S A 99:4156-60
Hatcher, M E; LeTrong, I; Stenkamp, R et al. (2001) Local dynamics of the CpG step in a DNA crystal. J Am Chem Soc 123:8874-5
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
Geahigan, K B; Meints, G A; Hatcher, M E et al. (2000) The dynamic impact of CpG methylation in DNA. Biochemistry 39:4939-46
Paz, M M; Sigurdsson, S T; Hopkins, P B (2000) Monoalkylation of DNA by reductively activated FR66979. Bioorg Med Chem 8:173-9
Okonogi, T M; Alley, S C; Reese, A W et al. (2000) Sequence-dependent dynamics in duplex DNA. Biophys J 78:2560-71

Showing the most recent 10 out of 102 publications