A Novel Role of Chromodomain Protein CBX8 in DNA Damage Response

Abstract Induction of DNA damage induces a dynamic repair process involving DNA repair factors and epigenetic regulators. Chromatin alterations must occur in order for DNA repair factors to gain access to DNA lesions and restore original chromatin configuration to preserve the gene expression profile. We characterize the novel role of CBX8, a chromodomain-containing protein with established roles in epigenetic regulation in DNA damage response. CBX8 protein rapidly accumulates at the sites of DNA damage within 30 seconds and progresses to accumulate until 4 minutes before gradually dispersing back to its pre-damage distribution by 15 minutes. CBX8 recruitment to the sites of DNA damage is dependent upon PARP1 activation and not dependent on ATM activation. CBX8 biochemically interacts with TRIM33, and its recruitment to DNA damage is also dependent on the presence of TRIM33. Knockdown of CBX8 using siRNA significantly reduces the efficiency of both homologous and the other non-homologous recombination as well as increases sensitivity of cells to ionizing radiation. These findings demonstrate that CBX8 functions in the PARP-dependent DNA damage response partly through interaction with TRIM33, and is required for efficient DNA repair.