Speaker
Description
Since 10 years, our lab has been developing a mechanistic model of the individual stress response based on the nucleo-shuttling of the ATM protein kinase. First, the stress triggers the monomerization of the ATM protein proportionally to the stress dose. Second, the ATM monomers diffuse to the nucleus to trigger the DNA repair pathways. Any delay caused by some environmental molecules or overexpressed proteins that interact with ATM may lead to a well-described pathology. Interestingly, we have observed that perinuclear interactions of ATM lead systematically to syndromes related to aging or neurodegeneration. Indeed, a crown of complexes made of ATM and some other specific proteins or molecules may forbid the entry of the nucleus to ATM: as a consequence, DNA breaks are neither recognized nor repaired, and progressively, cells die via senescence. A mathematical model describing the formation of ATM crowns and the senescence of cells is proposed.
