Filamentous nuclear actin regulation of PML NBs during the DNA damage response is deregulated by prelamin A

Abstract: Nuclear actin participates in a continuously expanding list of core processes within eukaryotic nuclei, including the maintenance of genomic integrity. In response to DNA damage, nuclear actin polymerises into filaments that are involved in the repair of damaged DNA through incompletely defined mechanisms. We present data to show that the formation of nuclear F-actin in response to genotoxic stress acts as a scaffold for PML NBs and that these filamentous networks are essential for PML NB fission and recruitment of microbodies to DNA lesions. Further to this, we demonstrate that the accumulation of the toxic lamin A precursor prelamin A induces mislocalisation of nuclear actin to the nuclear envelope and prevents the establishment of nucleoplasmic F-actin networks in response to stress. Consequently, PML NB dynamics and recruitment to DNA lesions is ablated, resulting in impaired DNA damage repair. Inhibition of nuclear export of formin mDia2 restores nuclear F-actin formation by augmenting polymerisation of nuclear actin in response to stress and rescues PML NB localisation to sites of DNA repair, leading to reduced levels of DNA damage

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Cell death & disease. - 13, 12 (2022) , 1042, ISSN: 2041-4889

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2022
Urheber
Cobb, Andrew M.
Silva, Shanelle A. de
Hayward, Robert
Sek, Karolina
Ulferts, Svenja
Grosse, Robert
Shanahan, Catherine

DOI
10.1038/s41419-022-05491-4
URN
urn:nbn:de:bsz:25-freidok-2321705
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:54 MEZ

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  • 2022

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