Differential stability of DNA crossovers in solution mediated by divalent cations

The assembly of DNA duplexes into higher-order structures plays a major role in many vital cellular functions such as recombination, chromatin packaging and gene regulation. However, little is currently known about the molecular structure and stability of direct DNADNA interactions that are required for such functions. In nature, DNA helices minimize electrostatic repulsion between double helices in several ways. Within crystals, B-DNA forms either right-handed crossovers by groovebackbone interaction or left-handed crossovers by groovegroove juxtaposition. We evaluated the stability of such crossovers at various ionic concentrations using large-scale atomistic molecular dynamics simulations. Our results show that right-handed DNA crossovers are thermodynamically stable in solution in the presence of divalent cations. Attractive forces at short-range stabilize such crossover structures with inter-axial separation of helices less than 20 . Right-handed crossovers, however, dissociate swiftly in the presence of monovalent ions only. Surprisingly, left-handed crossovers, assembled by sequence-independent juxtaposition of the helices, appear unstable even at the highest concentration of Mg2+studied here. Our study provides new molecular insights into chiral association of DNA duplexes and highlights the unique role divalent cations play in differential stabilization of crossover structures. These results may serve as a rational basis to understand the role DNA crossovers play in biological processes

Sur deux points aveugles de la doctrine juridique: nouvelles considérations sur le dialogisme normatif

C’est ainsi. Je ne me souviens pas que depuis ce déjeuner de la fin de l’hiver 90, depuis cette rencontre et nos premières discussions à l’ombre du Panthéon évoquées par André Lajoie au début de son étude intitulée « dans l’angle mort de l’analyse systémale », nous ayons jamais vraiment interrompu la conversation qui nous avait réunis ce jour-là et qui, depuis, se poursuit autour des thèmes qu’elle sait si bien cerner et auxquels elle apporte toujours, à la fois, toute sa rigueur critique et toute sa créativité théorique. Je voudrais donc que l’article qui suit soit un des moments de ce dialogue – de ce dialogue et de cet échange amical que j’entretiens avec Andrée Lajoie et qui, sous toutes ses formes, se prolonge – pour mon plus grand plaisir et mon plus grand profit – depuis maintenant plus de quinze ans

DNA-DNA Recognition: From Tight Contact to Fatal Attraction

International audienc

Les principes généraux du droit français de la fonction publique

In France, public service rests upon the fundamental rule of the specialization of the law applicable to public servants. This entails that public servants are given a special status that singles them out from others in the other economic or social sectors. That special legal status of the French public service is however being diminished under the influence of external factors. Economic factors tend to subject public servants to the general law of labour contracts. Political factors tend to give public servants the complete enjoyment of fundamental rights and civil liberties. Finally, administrative factors such as policies favouring mobility and promotion tend to lessen the importance of rigid classification and grading. On the eve of major statutory changes in the law of the public service in Québec, Professor Timsit’s study provides an interesting comparative viewpoint

Attributable cost of methicillin resistance: an issue that is difficult to evaluate

Estimating the consequences and the cost of methicillin resistance is a difficult challenge. Patients who develop methicillin-resistant ventilator-associated pneumonia (VAP) are very different from those who develop methicillin-sensitive VAP, and biased estimates are frequent. We reviewed some important confounding factors of which the reader should be aware