Conformations of Nicked and Gapped DNA Structures by NMR and Molecular Dynamic Simulations in Water
We have analyzed and compared the molecular structures and dynamics of DNA duplexes containing a nick or a gap of one nucleotide where the base in front of the gap is a guanine. The continuous strand has the sequence 5‘(CAGAGTCXCTGGCTC) where the residue X is absent for the nick, 14-mer, and where i...
Saved in:
Published in | Biochemistry (Easton) Vol. 37; no. 12; pp. 4059 - 4070 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
24.03.1998
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | We have analyzed and compared the molecular structures and dynamics of DNA duplexes containing a nick or a gap of one nucleotide where the base in front of the gap is a guanine. The continuous strand has the sequence 5‘(CAGAGTCXCTGGCTC) where the residue X is absent for the nick, 14-mer, and where it is a G residue for the gap. Duplexes were formed with the two corresponding 7-mers. Neither of these is phosphorylated adjacent at the nick site, but it is a good model for a single strand break. For the nick structure, the quantitative NMR data show that the global conformation is very close to canonical B-form DNA, but it displays enhanced local flexibility. For the gap structure, we observe only one species in which the extra G is well stacked into the helix. The two half-helices around this residue also show a B-form conformation. As with the nick duplex, the adjacent G imino protons show enhanced exchange with solvent. The gap does not close completely. Using distance constraints, MD calculations show that the nick conformation is very close to a duplex with no lesion but is indeed more flexible in the central part. The gapped structure shows two families of conformations. One is close to B-DNA, the other is significantly kinked at the gap which reduces the size of the cavity. We observe a spine of hydration within the cavities, similar, but of different geometry in the two cases. |
---|---|
Bibliography: | ark:/67375/TPS-KBX1NP4N-8 This work was, in part, financed by a grant from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche, ACC-SV8. istex:80BCE493F814CC7F98759DA9FCC61401D9AF848A ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/bi972377w |