Conformations and dynamics of the phosphodiester backbone of a DNA fragment that bears a strong topoisomerase II cleavage site
| Autor: | Saïd El Antri, Olivier Mauffret, Brigitte René, Grégoire Masliah, Serge Fermandjian |
|---|---|
| Přispěvatelé: | Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Bioorganique et Analytique, Faculté des Sciences et Techniques |
| Rok vydání: | 2007 |
| Předmět: |
Stereochemistry
MESH: DNA Topoisomerases Type II MESH: Base Sequence 010402 general chemistry Cleavage (embryo) 01 natural sciences 03 medical and health sciences Molecular dynamics chemistry.chemical_compound MESH: Esters Materials Chemistry A-DNA [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Physical and Theoretical Chemistry 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology Base Sequence Topoisomerase MESH: DNA Esters DNA 0104 chemical sciences Surfaces Coatings and Films Crystallography MESH: Nucleic Acid Conformation DNA Topoisomerases Type II chemistry Deoxyribose Phosphodiester bond biology.protein Nucleic Acid Conformation Counterion |
| Zdroj: | Journal of Physical Chemistry B Journal of Physical Chemistry B, American Chemical Society, 2007, 111 (16), pp.4235-43. ⟨10.1021/jp0683115⟩ |
| ISSN: | 1520-6106 1520-5207 |
| DOI: | 10.1021/jp0683115⟩ |
| Popis: | International audience; The dynamics of the DNA phosphodiester backbone conformations have been studied for a strong topoisomerase II cleavage site (site 22) using molecular dynamics simulations in explicit water and in the presence of sodium ions. We investigated the backbone motions and more particularly the BI/BII transitions involving the epsilon and zeta angles. The consensus cleavage site is adjacent to the phosphate which shows the most important phosphodiester backbone flexibility in the sequence. We infer that these latter properties could be responsible for the preferential cleavage at this site possibly through the perturbation of the cleavage/ligation activities of the topoisomerase II. More generally, the steps pur-pur and pyr-pur are those presenting the highest BII contents. Relations are observed between the backbone phosphodiester BI/BII transitions and the flexibility of the deoxyribose sugar and the helical parameters such as roll. The roll is sequence dependent when the related phosphate is in the BI form, whereas this appears not to be true when it is in the BII form. The BI/BII transitions are associated with water migration, and new relations are observed with counterions. Indeed, it is observed that a strong coupling exists between the BII form and the presence of sodium ions near the adjacent sugar deoxyribose. The presence of sodium ions in the O4' surroundings or their binding could assist the BI to BII transition by furnishing energy. The implications of these new findings and, namely, their importance in the context of the sequence-dependent behavior of BI/BII transitions will be investigated in future studies. |
| Databáze: | OpenAIRE |
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