AbstractsAstronomy & Space Science

The three-dimensional organization of the chromatin fiber is driven by entropy. Therefore, the folding of the chromatin fiber is essentially a problem of statistical physics. In the present thesis, two questions in the context of chromatin folding which are still not fully understood are investigated: on the one hand the organization of chromatin in mitosis and on the other hand the changes of chromatin organization in the damage response to ionizing radiation. In the first part we develop a model that explains the condensation of mitotic chromosomes by size-restricted dynamic looping of the chromatin fiber. Our results show also that chromatin loops can contribute to the experimentally determined bending rigidity of mitotic chromatids and generate the correct force-extension behaviour. In a next step, this folding model is then extended to describe sister chromatids by including dynamic binding and unbinding of sister fibers. We assess the interplay between cohesion and condensation and show that alignment and cohesion of sister chromatids requires detailed control of the abundance of tethering points between them. In the second part we examine the damage response of interphase chromosomes. With an expression-dependent folding model and utilizing experimental data on the transcriptional activity of cells that were exposed to ionizing radiation, we first show that the overall organization of chromatin does not change after irradiation. By modeling actual fiber breaks in local environments we demonstrate that broken ends are passively transported to the surface of their domains and that this facilitates recognition of the break by diffusing proteins. Finally, we use a graph theoretical approach to analyze the structural changes of histone positions in localization microscopy images of cells that were exposed to ionizing radiation. We validate our previous results that no changes of the overall organization of chromatin is recognizable and demonstrate that highly packaged heterochromatic areas of the genome decondense upon irradiation. Entropie steuert die dreidimensionale Organisation der Chromatinfaser. Die Faltung der Chromatinfaser ist daher grundsätzlich eine Aufgabenstellung für die Statistische Physik. Die vorliegende Dissertation untersucht zwei Fragen im Zusammenhang mit der Chromatinfaltung, welche noch immer nicht vollständig geklärt sind: Einerseits die Organisation der Chromatinfaser in der Mitose, andererseits die Änderung der Organisation vom Chromosomen bei der Reaktion auf Strahlungsschäden. Im ersten Teil haben wir ein Modell entwickelt, welches die Kondensation von Chromosomen in der Mitose durch dynamische und in ihrer Größe begrenzte Bildung von Schleifen erklärt. Unsere Ergebnisse zeigen, dass Schleifen der Chromatinfaser einen Beitrag zur experimentell ermittelten iegesteifigkeit von Chromosomen leisten können und die korrekte Kraftauslenkungscharakteristik erzeugen. Im nächsten Schritt haben wir das Faltungsmodell durch die Einbeziehung von dynamischem Binden und Wiederablösen zwischen…