A single formula to describe radiation-induced protein relocalization: Towards a mathematical definition of individual radiosensitivity

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 seve...

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Veröffentlicht in:Journal of theoretical biology 2013-09, Vol.333, p.135-145
Hauptverfasser: Bodgi, Larry, Granzotto, Adeline, Devic, Clément, Vogin, Guillaume, Lesne, Annick, Bottollier-Depois, Jean-François, Victor, Jean-Marc, Maalouf, Mira, Fares, Georges, Foray, Nicolas
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Sprache:eng
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Zusammenfassung: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. •A number of stress response proteins relocalize in nucleus as identifiable foci.•We propose a single formula to describe appearance/disappearance kinetics of foci.•The parameters of the Bodgi's function allows to define radiosensitivity.
ISSN:0022-5193
1095-8541
DOI:10.1016/j.jtbi.2013.05.020