Anillin-dependent actin assembly at PML NBs protects genome stability

Nuclear filamentous actin (F-actin) is emerging as a key regulator of genome stability ^1–6 . During replication stress, transient bursts of nuclear actin assembly in S-phase promote fork remodelling and repair ^3,4 , but how these bursts are initiated, regulated, and whether nuclear F-actin also act on DNA lesions inherited across cell cycles, remains unknown.

Here, we show that replication stress induces nuclear actin assembly at liquid-liquid phase-separated (LLPS) promyelocytic leukaemia nuclear bodies (PML NBs), driven by the actin-binding protein Anillin. Although best known as a cytokinesis factor, Anillin localises to PML NBs in interphase, where it concentrates monomeric actin (G-actin) and establishes a favourable environment for spontaneous actin assembly. Filament growth within these condensates remodels PML NB morphology and composition, releasing sequestered AKT into the nucleoplasm. AKT is subsequently phosphorylated and activated, and this nuclear AKT activity is required to regulate 53BP1 nuclear bodies in G1. These protective LLPS compartments shield under-replicated DNA inherited from the stressed S-phase until the following S-phase. This prevents premature engagement by aberrant repair pathways that would otherwise generate toxic intermediates and culminate in mitotic failure.

Together, these findings define a condensate-to-filament pathway in which nuclear F-actin dynamically reorganises phase-separated compartments to safeguard genome stability across cell cycles.