Role of nuclear actin filaments in DNA repair dynamics

Abstract

Actin filaments (F-actin) have well-known functions in the cytoplasm, including generating forces for cell movement and enabling myosin-driven dynamics of vesicles and mRNAs. In addition, the recent development of innovative tools for F-actin detection have revealed dynamic and transient filaments in the nuclei, which form in response to specific stimuli. Here we provide an overview of the functions of F-actin and myosins in nuclei, with a focus on their role in DNA repair and genome stability. We emphasize recent discoveries of nuclear F-actin driving the relocalization of heterochromatic repair sites to the nuclear periphery for ‘safe' homologous recombination (HR) repair of double-strand breaks (DSBs). F-actin also promotes repair focus clustering and DSB resection in euchromatin, facilitating HR progression. We highlight regulatory mechanisms specialized for actin polymerization during DNA replication and repair, and emphasize recent studies revealing alternative motors for the directional movement of repair sites. Together, these discoveries challenge previous models that actin is substantially monomeric in the nucleus and that DSBs move via Brownian motion, revealing a complex network of dynamic filaments, motors and regulators, coordinating chromatin dynamics with repair progression.