Temporal Control of Cellular Function: From DNA Repair to Organelle Division

by Alessandra Lucchetti (Niels Bohr Institute - University of Copenhagen)

Tuesday 9 Sept 2025, 14:30 → 15:30 Europe/Rome

1/1-2 - Aula "C. Voci" (Dipartimento di Fisica e Astronomia - Edificio Marzolo)

Cells use dynamic regulation to respond to stress, control gene
expression, and organize internal structures. In this seminar, I will
present three studies that explore how time-dependent processes shape
biological outcomes. First, we show how oscillations in the transcription
factor p53 enhance DNA repair by coordinating the formation of repair foci
through phase separation [1]. Second, we investigate the p53 oscillator as
a nonlinear system, demonstrating its ability to entrain to external
perturbations and exhibit complex behaviors such as multi-stability,
mode-hopping and period-doubling [2]. Finally, I will share ongoing work
on the algal pyrenoid, a CO₂-fixing organelle, where mechanical and
biochemical regulation appear to govern its division through phase
separation [3]. Together, these studies highlight how dynamic signaling
and physical mechanisms interact to control cellular function.

[1] Heltberg, M. S., Lucchetti, A., Hsieh, F. S., Nguyen, D. P. M., Chen,
S. H., & Jensen, M. H. (2022). Enhanced DNA repair through droplet
formation and p53 oscillations. Cell, 185(23), 4394-4408.

[2] Jiménez, A., Lucchetti, A., Heltberg, M. S., Moretto, L., Sanchez, C.,
Jambhekar, A., ... & Lahav, G. (2024). Entrainment and multi-stability of
the p53 oscillator in human cells. Cell Systems, 15(10), 956-968.

[3] Lucchetti, A., Jensen, M. H. & Heltberg, M. S., Post-Translational
Modifications Govern Dynamics of CO2-fixing organelle during Fission, In
preparation