NMR Study of A Heterochiral DNA Hairpin: Impact of L-Enantiomery in the Loop

We carried out a structural study of the DNA heterochiral strand d (AGCTTATCAT(L)CGATAAGCT), -AT(L)C-, where T(L) (L thymine) replaces T (natural D-thymine). -AT(L)C- is a structural analog of -ATC- that belongs to a strong topoisomerase II DNA cleavage site and which has been shown to resolve into...

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Published inJournal of biomolecular structure & dynamics Vol. 19; no. 3; pp. 459 - 470
Main Authors Amri, C. El, Mauffret, O., Santamaria, F., Tevanian, G., Rayner, B., Fermandjian, S.
Format Journal Article
LanguageEnglish
Published England Taylor & Francis Group 01.12.2001
Taylor & Francis: STM, Behavioural Science and Public Health Titles
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Summary:We carried out a structural study of the DNA heterochiral strand d (AGCTTATCAT(L)CGATAAGCT), -AT(L)C-, where T(L) (L thymine) replaces T (natural D-thymine). -AT(L)C- is a structural analog of -ATC- that belongs to a strong topoisomerase II DNA cleavage site and which has been shown to resolve into a hairpin structure with a stem formed by eight Waston-Crick base-pairs and a single residue loop closed by an A.C sheared base-pair. Although -AT(L)C-, like its parent -ATC-, folds into a hairpin structure at low and high DNA concentrations it displays a lower stability (Tm of 56 °C versus 58.5 °C). Several NMR features in-AT(L)C- account for the disruption of the A.C pairing in the loop and a weakening of the C.G base-pair stability at the stem-loop junction. For instance, the exchange of the loop imino protons with solvent is accelerated compared with the natural oligonucleotide -ATC-. The higher flexibility of the heterochiral loop is confirmed by the results of NMR restrained molecular dynamics. In the calculated final structures of-AT(L)C-, the T10(L) residue moves the A9 and C11 residues away, thus preventing the loop closure through a C.A sheared base-pair and the achievement of a good base-base or sugarbase stacking. Actually, most of the stabilizing interactions present in -ATC- are lost in the heterochiral -AT(L)C- explaining its weaker stability.
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ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2001.10506754