Mathematical Modelling of DNA Replication Reveals a Trade-off between Coherence of Origin Activation and Robustness against Rereplication

Eukaryotic genomes are duplicated from multiple replication origins exactly once per cell cycle. In Saccharomyces cerevisiae, a complex molecular network has been identified that governs the assembly of the replication machinery. Here we develop a mathematical model that links the dynamics of this network to its performance in terms of rate and coherence of origin activation events, number of activated origins, the resulting distribution of replicon sizes and robustness against DNA rereplication. To parameterize the model, we use measured protein expression data and systematically generate kinetic parameter sets by optimizing the coherence of origin firing. While randomly parameterized networks yield unrealistically slow kinetics of replication initiation, networks with optimized parameters account for the experimentally observed distribution of origin firing times. Efficient inhibition of DNA rereplication emerges as a constraint that limits the rate at which replication can be initiated. In addition to the separation between origin licensing and firing, a time delay between the activation of S phase cyclin-dependent kinase (S-Cdk) and the initiation of DNA replication is required for preventing rereplication. Our analysis suggests that distributive multisite phosphorylation of the S-Cdk targets Sld2 and Sld3 can generate both a robust time delay and contribute to switch-like, coherent activation of replication origins. The proposed catalytic function of the complex formed by Dpb11, Sld3 and Sld2 strongly enhances coherence and robustness of origin firing. The model rationalizes how experimentally observed inefficient replication from fewer origins is caused by premature activation of S-Cdk, while premature activity of the S-Cdk targets Sld2 and Sld3 results in DNA rereplication. Thus the model demonstrates how kinetic deregulation of the molecular network governing DNA replication may result in genomic instability

Histoire et sylviculture aujourd'hui : l'exemple des taillis de la forêt de Lamotte-Beuvron en Sologne

ABSTRACT The present work was undertaken in order to determine the age of Sweet Chestnut coppice stumps in a state forest in the French Sologne region (central France). The final aim was to find a relationship between the age of plantation and actual wood production. This biological research lead us to a historical investigation. The study of land-use during the past 150 years gave indications on the history of the whole forest area, giving the age of Chestnut stumps with a satisfactory precision. During this period, rural land-use was modified : in a first stage agro- silvo-pastoral practices were quite extensive, then the purchase of the wooded area by Forest Administration lead to an intensive land-use, exclusively forest-oriented, with an increasing interest in game management, excluding rural populations from the area. This evolution is described in a regional context, and local restrictions allowing these changes are then analyzed. In a final stage, several agricultural and silvicultural management practices are analyzed in more detail at the wood-lot level.RÉSUMÉ Afin de donner un âge à des souches de châtaigniers traités en taillis dans une forêt domaniale de Sologne, pour trouver un lien entre la production actuelle de bois et la date de plantation, nous avons été conduits à faire des recherches historiques. En étudiant les occupations des sols au cours des 150 dernières années, nous avons pu retracer l'histoire du massif forestier de Lamotte-Beuvron et donner avec une précision suffisante l'âge de souches de châtaignier. Durant cette période, il y a eu transformation de l'utilisation de l'espace rural : d'abord un usage extensif avec des pratiques agro-sylvo-pastorales, ensuite, lors de l'acquisition de la partie boisée par l'Administration Forestière, un usage intensif à vocation exclusivement forestière, puis cynégétique, excluant défait les populations rurales de cet espace. Nous retraçons cette évolution en plaçant ce massif forestier dans un cadre régional, puis en analysant les contraintes locales qui ont rendu possible ce changement. Enfin, en descendant au niveau de la parcelle forestière, nous analysons encore plus finement certains points de gestion agricole et sylvicole.Bedeneau M, Nougarède O., Cabanettes A. Histoire et sylviculture aujourd'hui : l'exemple des taillis de la forêt de Lamotte-Beuvron en Sologne. In: Norois, n°153, Janvier-Mars 1992. pp. 57-80

Fate of the nucleolar vacuole during resumption of cell cycle in pea cotyledonary buds

Meristematic cells of pea cotyledonary buds blocked in G(0-1) state contain a small nucleolus with a large central clear area surrounded by a fibrillar rim. The nucleolar structure varies according to the cell cycle from the G(0-1)-blocked state until the first mitoses occurring between 24 and 27 h after removal of the main stem. In order to better identify and understand the role of the central area in the nucleolar function, its content was investigated by cytochemical and terminal deoxynucleotidyl transferase-immunogold methods. The central area showed the characteristics of a vacuole commonly constituted of the condensed chromatin, ribonucleoprotein granules, and lack of argyrophilic proteins. 3 h alter decapitation, a thickening of the fibrillar rim occurred, accompanied by an increase of granules in the vacuole. After 6 h, the unique vacuole broke up into two to four small vacuoles in which the granules are more abundant. After 12 h the nucleolus acquired compact structure with few minute vacuoles dispersed over the fibrillar component. During the whole cell cycle, the condensed chromatin is always observed in the vacuole. Our findings suggest that the appearance of the vacuoles is subsequent to the output of preribosomes from nucleolus. These vacuoles might play a role in condensation and decondensation of the chromatin