Enhanced DNA repair through droplet formation and p53 oscillations.
DNA repair
Ostwald ripening
droplets
oscillations
p53 dynamics
phase transitions
response
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
10 11 2022
10 11 2022
Historique:
received:
13
04
2022
revised:
23
08
2022
accepted:
05
10
2022
entrez:
11
11
2022
pubmed:
12
11
2022
medline:
16
11
2022
Statut:
ppublish
Résumé
Living organisms are constantly exposed to DNA damage, and optimal repair is therefore crucial. A characteristic hallmark of the response is the formation of sub-compartments around the site of damage, known as foci. Following multiple DNA breaks, the transcription factor p53 exhibits oscillations in its nuclear concentration, but how this dynamics can affect the repair remains unknown. Here, we formulate a theory for foci formation through droplet condensation and discover how oscillations in p53, with its specific periodicity and amplitude, optimize the repair process by preventing Ostwald ripening and distributing protein material in space and time. Based on the theory predictions, we reveal experimentally that the oscillatory dynamics of p53 does enhance the repair efficiency. These results connect the dynamical signaling of p53 with the microscopic repair process and create a new paradigm for the interplay of complex dynamics and phase transitions in biology.
Identifiants
pubmed: 36368307
pii: S0092-8674(22)01319-8
doi: 10.1016/j.cell.2022.10.004
pii:
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
Proto-Oncogene Proteins c-mdm2
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4394-4408.e10Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no conflict of interests.