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Structure of a bent DNA: two-dimensional NMR studies on d(GAAAATTTTC)/sub 2/
Document Type
Journal Article
Author
Source
Biochemistry; (United States); 27:9
Subject
62 RADIOLOGY AND NUCLEAR MEDICINE DNA
CONFORMATIONAL CHANGES
NUCLEAR MAGNETIC RESONANCE
CHEMICAL SHIFT
HEAVY WATER
STEREOCHEMISTRY
HYDROGEN COMPOUNDS
MAGNETIC RESONANCE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
RESONANCE
WATER 550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
Language
English
Abstract
Intrinsic DNA bending is caused by specific DNA sequences. The decamer d(GA/sub 4/T/sub 4/C)/sup 2/, when it repeats in a synthetic polymer or in kinetoplast DNA, results in a macroscopic bending of the molecule as a whole. The authors employed high-resolution two-dimensional NMR methods to examine the intrinsic structural properties of the d(GA/sub 4/T/sub 4/C)/sub 2/ duplex in solution. Examination of the NOESY data at 50- and 100-ms mixing times indicated that the kinds of observed NOEs can originate if each of the ten nucleotidyl residues belong to the B-DNA family, i.e., C2'-endo, anti. However, the degree of observed NOE intensities from the A-T junction as well as the observed AH2-AH2 cross-peaks from adjacent AT pairs could not be rationalized on the basis of a straight B-DNA model but could be explained by only a B-DNA model with some structural discontinuity at the A-T junction-the site of 2-fold symmetry in the molecule. In view of the fact that the degree of observed NOE intensities can be complicated spin diffusion and by fine structural distortion, they have resorted to the use of quantitative theoretical NOESY simulation to delineate the structural discontinuity at the A-T junction and to arrive at a structure for the duplex d(GA/sub 4/T/sub 4/C)/sub 2/. They propose a junction B-DNA model which can quantitatively explain the 2D NOESY data at 100- and 50-ms mixing times. It is the thesis of this paper that the observed bending in polymers with a repeat of d(GA/sub 4/T/sub 4/C)/sub 2/ and the bending in natural DNAs where A/sub n/T/sub n/(centered dot)A/sub n/T/sub n/ repeats are present originate at the oligonucleotide repeat level.