Nuclear actin polymerization rapidly mediates replication fork remodeling upon stress by limiting PrimPol activity
Abstract: Cells rapidly respond to replication stress actively slowing fork progression and inducing fork reversal. How replication fork plasticity is achieved in the context of nuclear organization is currently unknown. Using nuclear actin probes in living and fixed cells, we visualized nuclear actin filaments in unperturbed S phase and observed their rapid extension in number and length upon genotoxic treatments, frequently taking contact with replication factories. Chemically or genetically impairing nuclear actin polymerization shortly before these treatments prevents active fork slowing and abolishes fork reversal. Defective fork remodeling is linked to deregulated chromatin loading of PrimPol, which promotes unrestrained and discontinuous DNA synthesis and limits the recruitment of RAD51 and SMARCAL1 to nascent DNA. Moreover, defective nuclear actin polymerization upon mild replication interference induces chromosomal instability in a PRIMPOL-dependent manner. Hence, by limiting PrimPol activity, nuclear F-actin orchestrates replication fork plasticity and is a key molecular determinant in the rapid cellular response to genotoxic treatments
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Nature communications. - 14, 1 (2023) , 7819, ISSN: 2041-1723
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2023
- Urheber
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Palumbieri, Maria Dilia
Merigliano, Chiara
González-Acosta, Daniel
Kuster, Danina
Krietsch, Jana
Stoy, Henriette
Känel, Thomas von
Ulferts, Svenja
Welter, Bettina
Frey, Joël
Doerdelmann, Cyril
Sanchi, Andrea
Grosse, Robert
Chiolo, Irene
Lopes, Massimo
- DOI
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10.1038/s41467-023-43183-5
- URN
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urn:nbn:de:bsz:25-freidok-2416981
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:57 MEZ
Datenpartner
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Beteiligte
- Palumbieri, Maria Dilia
- Merigliano, Chiara
- González-Acosta, Daniel
- Kuster, Danina
- Krietsch, Jana
- Stoy, Henriette
- Känel, Thomas von
- Ulferts, Svenja
- Welter, Bettina
- Frey, Joël
- Doerdelmann, Cyril
- Sanchi, Andrea
- Grosse, Robert
- Chiolo, Irene
- Lopes, Massimo
- Universität
Entstanden
- 2023
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