Modello per lo studio dell'organizzazione tridimensionale nei cromosomi durante la replicazione del DNA

In Eukaryotes, DNA is tightly packed into a polymer-like structure called chromatin. Chromatin self-organization remains an elusive phenomenon whose impact is extensive in several cells’ fundamental processes. Numerous biological evidence suggest how 3D chromosome organization plays a decisive role in the maintenance, transcription and transmission of the genetic code. Here we focus on the specific problem of how chromatin folding couples with DNA replication dynamics. Taking into account chromosomes’ conformation properties is in fact crucial to fully characterize the one dimensional process of eukaryotic genomes’ replication. Modeling of chromatin folding and replication dynamics has been instrumental in gaining knowledge on their underlying mechanisms but apparently no model has attempted to combine the two. For this reason, we used polymer modelling to fill this gap by implementing a polymer class capable of replicating itself starting from several origins of replication. The aim of this thesis is to introduce this new implementation and show how the tuning of its parameters enables one to simulate realistic biological settings. In particular, this framework was applied to investigate the formation of replication factories and the role of pairing between newly replicated chromatids in Saccharomyces cerevisiae. The preliminary results suggest that the model is indeed effective in analyzing in silico conformation properties of replicating chromosomes and how it could serve as foundation for future studies on more complex scenarios.