γ-tubulin mediates DNA double-strand break repair.

Abstract

Double-strand breaks (DSBs) in DNA pose a critical threat to genomic integrity, potentially leading to the onset and progression of various diseases, including cancer. Cellular responses to such lesions entail sophisticated repair mechanisms primarily mediated by non-homologous end joining (NHEJ) and homologous recombination (HR). Interestingly, the efficient recruitment of repair proteins and completion of DSB repair likely involve complex, inter-organelle communication and coordination of cellular components. In this study, we report a role of γ-tubulin in DSB repair. γ-tubulin is a major microtubule nucleation factor governing microtubule dynamics. We show that γ-tubulin is recruited to the site of DNA damage and is required for efficient DSB repair via both NHEJ and HR. Suppression of γ-tubulin impedes DNA repair and exacerbates DNA damage accumulation. Furthermore, γ-tubulin mediates the mobilization and formation of DNA damage foci, which serve as repair centers, thereby facilitating the recruitment of HR and NHEJ repair proteins on damaged chromatin. Finally, pharmacological inhibition of γ-tubulin enhances the cytotoxic effect of DNA-damaging agents, consistent with the DNA repair function of γ-tubulin, and underscoring the potential of its therapeutic intervention in cancer therapy.