Maria Molano I Fernandez

• Præsentation

My PhD project currently aims at investigating replication catastrophe in vivo by using Drosophila as a model system.

The genome of all proliferating cells must be faithfully replicated before every cell division. Nevertheless, cells are constantly exposed to both endogenous and exogenous insults that can impair DNA replication, thus leading to replication stress. In these conditions, there is an increase in ssDNA that is rapidly bound to RPA to protect it from degradation. This eventually leads to the activation of the ATR checkpoint, which stabilizes replication forks and inhibits replication to prevent genome instability. When the source of replication stress persists or is very strong, cells undergo pan-nuclear DNA damage and eventually die. This phenomenon is known as replication catastrophe.

Studies performed in mammalian in vitro systems have demonstrated that RPA exhaustion initiates the process of replication catastrophe. That is, cells can survive as long as there is enough RPA to protect all ssDNA. However, if the RPA pool is depleted, unprotected ssDNA accumulates, resulting in extensive DNA damage.

We are currently modelling replication catastrophe in Drosophila and hope to study the cellular responses to this process in vivo.