Soutenance de Dario D'Asaro
| When |
Dec 04, 2024
from 02:00 to 04:00 |
|---|---|
| Where | Salle des thèses |
| Contact Name | Dario D'Asaro |
| Attendees |
Dario D'Asaro |
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A fundamental aspect of cellular function is the accurate duplication of the genome and the preparation of resulting DNA copies for efficient cell division. How these complex tasks are achieved within the highly hierarchical 3D organization of chromatin remains elusive. In this thesis, we quantitatively examine how the active, out-of-equilibrium process of DNA replication influences 3D chromatin folding, using a computational approach based on polymer modeling.
First, we explore the spatial effects of the ring-like topology of replication bubbles growing within a linear polymer chain. This framework is later combined with realistic 1D replication dynamics to model the genome of Saccharomyces cerevisiae during S phase. Our model predicts “fountain” patterns on Hi-C maps, characteristic of interacting replication forks, and we confirm their presence in vivo by analyzing new experimental data.
Next, we investigate the spatial distribution of replication at the nuclear scale, explicitly incorporating the higher-level Rabl organization of the yeast genome. Finally, the model is used to predict the structure of sister chromatids and test different hypotheses regarding the establishment of cohesion. Notably, we demonstrate that asymmetrical cohesion more accurately reproduces the currently available Hi-C data.