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Résumé |
Cells must coordinate biochemical processes in crowded environments, and one of
their key strategies is the formation of biomolecular condensates. A central
question is how these condensates remain stable when many are formed
simultaneously as an integral part of the DNA damage response. Passive droplets
naturally undergo Ostwald ripening and coarsen over time, which is critical during
DNA damage, where multiple repair foci must coexist to ensure accurate genome
maintenance.
I investigate how we can characterize biomolecular condensates based in single-
particle data and how non-eqilibrium fluxes control condensate stability.
Developing a theoretical framework, I will show that the amplitude and period of
oscillations (like p53 in the DNA damage response) modulate material exchange
between condensates and thereby distribute resources across multiple DNA repair
foci,in order to circumvent Ostwald ripening. Our model explains how the
characteristic timescale of p53 dynamics optimizes the repair process, and we
predict that the occurrence of oscillations directly enhances DNA repair, which we
confirmed experimentally. We further expanded the model to include spatially
dependent addition and removal of condensate material, and analytically derived
how this out-of-equilibrium behaviour can stabilize multiple condensates.
Together, these findings reveal oscillatory signaling as a physical regulatory
principle: cells can tune the temporal dynamics of p53 to shape condensate
behavior, stabilize DNA repair foci, and enhance functional molecular responses.
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