Cyclin A2 is an essential regulator of the cell division cycle through the activation of kinases that participate to the regulation of S phase as well as the mitotic entry. However,whereas its degradation by the prote...Cyclin A2 is an essential regulator of the cell division cycle through the activation of kinases that participate to the regulation of S phase as well as the mitotic entry. However,whereas its degradation by the proteasome in mid mitosis was thought to be essential for mitosis to proceed,recent observations show that a small fraction of cyclin A2 persists beyond metaphase and is degraded by autophagy. Its implication in the control of cytoskeletal dynamics and cell movement has unveiled its role in the modulation of Rho A activity. Since this GTPase is involved in both cell rounding early in mitosis and later,in the formation of the cleavage furrow,this suggests that cyclin A2 is a novel actor in cytokinesis. Taken together,these data point to this cyclin as a potential mediator of cell-niche interactions whose dysregulation could be taken as a hallmark of metastasis.展开更多
Investigating average thermodynamic quantities is not sufficient to understand conformational transitions of a finite-size polymer. We propose that such transitions are better described in terms of the probability dis...Investigating average thermodynamic quantities is not sufficient to understand conformational transitions of a finite-size polymer. We propose that such transitions are better described in terms of the probability distribution of some finite-size order parameter, and the evolution of this distribution as a control parameter varies. We demonstrate this claim for the coil-globule transition of a linear polymer and its mapping onto a two-state model. In a biological context, polymer models delineate the physical constraints experienced by the genome at different levels of organization,from DNA to chromatin to chromosome. We apply our finite-size approach to the formation of plectonemes in a DNA segment submitted to an applied torque and the ensuing helix-coil transition that can be numerically observed, with a coexistence of the helix and coil states in a range of parameters. Polymer models are also essential to analyze recent in vivo experiments providing the frequency of pairwise contacts between genomic loci. The probability distribution of these contacts yields quantitative information on the conformational fluctuations of chromosome regions. The changes observed in the shape of the distribution when the cell type or the physiological conditions vary may reveal an epigenetic modulation of the conformational constraints experienced by the chromosomes.展开更多
基金Supported by Agence Nationale de la Recherche(08-BLAN-0037-02),Fondation ARC pour la Recherche sur le Cancerand Gefluc+2 种基金CNRS/Région Languedoc-Roussillon and Fondation pour la Recherche Médicale(Loukil A)the French Ministry of Education and Research and Fondation pour la Recherche Médicale(Bendris N)the Canadian Institutes of Health Research,La Ligue Contre le Cancer and the Fondation de France(Cheung CT)
文摘Cyclin A2 is an essential regulator of the cell division cycle through the activation of kinases that participate to the regulation of S phase as well as the mitotic entry. However,whereas its degradation by the proteasome in mid mitosis was thought to be essential for mitosis to proceed,recent observations show that a small fraction of cyclin A2 persists beyond metaphase and is degraded by autophagy. Its implication in the control of cytoskeletal dynamics and cell movement has unveiled its role in the modulation of Rho A activity. Since this GTPase is involved in both cell rounding early in mitosis and later,in the formation of the cleavage furrow,this suggests that cyclin A2 is a novel actor in cytokinesis. Taken together,these data point to this cyclin as a potential mediator of cell-niche interactions whose dysregulation could be taken as a hallmark of metastasis.
基金the program "Small Systems Nonequilibrium Fluctuations,Dynamics and Stochastics,and Anomalous Behavior" of the Kavli Institute for Theoretical Physics China at the Chinese Academy of Sciences(KITPC),held in Bejing in July 2013funded by the French Institut de la Recherche M'edicale,under Grant MICROMEGAS PC201104+1 种基金the French Institut National du Cancer,under Grant INCa-5960the French Agence Nationale de la Recherche under Grant No.ANR-13-BSV5-0010-03.UPMC belongs to Sorbonne Universit'es
文摘Investigating average thermodynamic quantities is not sufficient to understand conformational transitions of a finite-size polymer. We propose that such transitions are better described in terms of the probability distribution of some finite-size order parameter, and the evolution of this distribution as a control parameter varies. We demonstrate this claim for the coil-globule transition of a linear polymer and its mapping onto a two-state model. In a biological context, polymer models delineate the physical constraints experienced by the genome at different levels of organization,from DNA to chromatin to chromosome. We apply our finite-size approach to the formation of plectonemes in a DNA segment submitted to an applied torque and the ensuing helix-coil transition that can be numerically observed, with a coexistence of the helix and coil states in a range of parameters. Polymer models are also essential to analyze recent in vivo experiments providing the frequency of pairwise contacts between genomic loci. The probability distribution of these contacts yields quantitative information on the conformational fluctuations of chromosome regions. The changes observed in the shape of the distribution when the cell type or the physiological conditions vary may reveal an epigenetic modulation of the conformational constraints experienced by the chromosomes.
