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The biological functions played by the nucleus of eukaryotic cells and especially those involved in cellular differentiation not only depend on the genomic sequence but also on all the proteins which form the nucleo-protein complex named chromatin. The tridimensional organization of this huge polymer involves many structural levels, the most basic one being the nucleosome. Nucleosomes further organize into the so-called 30 nm fiber, which, according to recent works, is likely to be the main functional level of chromatin. We wish here to propose a plausible structure for the 30 nm chromatin fiber that could explain its functional role. In our model, silenced chromatin is locked by nucleosome stacking interactions. This is achieved by a conformational transition within the nucleosome core particle (NCP) which allows nucleosomes to stack along two helices without bending the DNA linkers. We used molecular modeling to check that this conformational transition was plausible. Then we proposed to modify the well-known two-angle model according to these atomic level results. The emerging picture is an allosteric behavior of the nucleosomes induced by their collective organization within the 30 nm chromatin fiber. [Copyright &y& Elsevier]

Cell survival is conventionally defined as the capability of irradiated cells to produce colonies. It is quantified by the clonogenic assays that consist in determining the number of colonies resulting from a known number of irradiated cells. Several mathematical models were proposed to describe the survival curves, notably from the target theory. The Linear-Quadratic (LQ) model, which is to date the most frequently used model in radiobiology and radiotherapy, dominates all the other models by its robustness and simplicity. Its usefulness is particularly important because the ratio of the values of the adjustable parameters, α and β , on which it is based, predicts the occurrence of post-irradiation tissue reactions. However, the biological interpretation of these parameters is still unknown. Throughout this review, we revisit and discuss historically, mathematically and biologically, the different models of the radiation action by providing clues for resolving the enigma of the LQ model. [ABSTRACT FROM AUTHOR]

Abstract: Immunofluorescence with antibodies against DNA damage repair and signaling protein is revolutionarising the estimation of the genotoxic risk. Indeed, a number of stress response proteins relocalize in nucleus as identifiable foci whose number, pattern and appearance/disappearance rate depend on several parameters such as the stress nature, dose, time and individual factor. Few authors proposed biomathematical tools to describe them in a unified formula that would be relevant for all the relocalizable proteins. Based on our two previous reports in this Journal (Foray et al., 2005; Gastaldo et al., 2008), we considered that foci response to stress is composed of a recognition and a repair phase, both described by an inverse power function provided from a Euler's Gamma distribution. The resulting unified formula called “Bodgi's function” is able to describe appearance/disappearance kinetics of nuclear foci after any condition of genotoxic stress. By applying the Bodgi's formula to DNA damage repair data from 45 patients treated with radiotherapy, we deduced a classification of human radiosensitivity based on objective molecular criteria, notably like the number of unrepaired DNA double-strand breaks and the radiation-induced nucleo-shuttling of the ATM kinase. [Copyright &y& Elsevier]