Facultat de

Medicina i Ciències de la Salut

El proper 10 de març a les 12 h l'Aula 11 del Campus Clínic acollirà el desè dels seminaris del Cicle Continuat de Conferències de la Facultat de Medicina i Ciències de la Salut. 

El seminari titulat "The sterol-PI4P exchange at the ER-Golgi contact sites controls the Tel1/ATM axis of the DNA Damage Response” i serà a càrrec de la Dra. Maria Moriel-Carretero, Researcher and Group Leader Centre de Recherche en Biologie Cellulaire  de Montpellier (CRBM-CNRS).

Aquest seminari s'adreça a tot el PDI de la Facultat de Medicina i Ciències de la Salut i als centres de recerca de Barcelona i no cal inscripció prèvia per assistir-hi.

A continuació, una breu sinopsi en anglès dels temes que hi abordarà:

"Genome integrity must be preserved to warrant cell fitness, therefore cells challenged with genotoxic stress activate the DNA damage response (DDR) to coordinate cell cycle arrest with DNA repair. This occurs within the cell nucleus and is therefore confined by the nuclear membrane. We tend to draw the nuclear membrane as a closed sphere only interrupted by the nuclear pores. Yet, the nuclear membrane is a continuum with the Endoplasmic Reticulum (ER), therefore we explored whether the biology of the ER was important for genome integrity preservation. We found that genotoxic stress triggers the birth of ER-derived lipid droplets that serve as a sink for sterols. In particular, we demonstrate by pharmacological and genetic approaches, both in S. cerevisiae and in cultured human cells, that the inability to remove sterols from the ER membrane maintains a permanent DDR activation, thus preventing downstream DNA repair and cell cycle resumption. Sterols remaining in the ER are known to boost forward the activity of OSBP1, a machine that, in exchange, translocates Phosphatidyl-Inositol-4-P (PI4P) from the Golgi to the ER. Since the master kinases of the DDR, ATM and ATR, are ancestral PIP-binders, we assessed whether the sterol / PI4P balance impacted them. We uncover that, since maintaining low sterol levels in the ER keeps high PI4P levels in the Golgi, Golgi-resident PI4P acts as a lock for ATM away from its nuclear duties, thus attenuating the DDR. On the contrary, elevating ER sterol levels, OSBP1 activity or PI4P hydrolysis triggers PI4P consumption, subsequently frees ATM and sustains a hyper-activated DDR. Thus, we bring the unprecedented notion that manipulating a lipid axis can directly impact on the degree of genome integrity. This challenges the current view of the DDR as a signaling cascade exclusively controlled by proteins. And opens new avenues, which I will highlight, motivating the study of lipids as masters of genome homeostasis."