UCSF

Nuclear actin filaments and actin regulators play a role in the DNA repair process.

The branched actin nucleator Arp2/3 has been identified as one such actin regulator and was found to localize to DNA double-stranded break sites and play a role in efficient homology-directed repair. Arp2/3’s cytoplasmic activities have been well-documented and studied, but its presence in the nucleus is only beginning to be understood. We asked whether Arp2/3 was binding directly to DNA for its role in DNA repair and whether it also played a role in the non-homologous end joining DNA repair pathway. We find that Arp2/3 binds directly to DNA and that binding is facilitated by its p41 subunit, with a preference for the p41b isoform. Additionally, this binding is mutually exclusive of Arp2/3’s ability to bind the VCA domain of its activator, leading to Arp2/3’s actin nucleating abilities remaining intact. In addition to the previously reported role of Arp2/3 in homology-directed repair, we present evidence that Arp2/3 is also required for effective non-homologous end joining.