title: 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 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 s and progresses to accumulate until 4 min before gradually dispersing back to its predamage distribution by 15 min. 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.
authors.affiliation: From the MD-PhD Program, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903.|the Department of Cellular and Molecular Pharmacology, Rutgers-Graduate School of Biomedical Sciences, Piscataway, New Jersey 08854.|the Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, and.|the Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03766.
authors.forename: Jay
authors.initials: J
authors.lastname: Oza
authors.affiliation: the Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, and.
authors.forename: Bratati
authors.initials: B
authors.lastname: Ganguly
authors.affiliation: the Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, and.
authors.forename: Atul
authors.initials: A
authors.lastname: Kulkarni
authors.affiliation: the Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, and.
authors.forename: Vasudeva
authors.initials: V
authors.lastname: Ginjala
authors.affiliation: the Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, and.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: the Department of Cellular and Molecular Pharmacology, Rutgers-Graduate School of Biomedical Sciences, Piscataway, New Jersey 08854, ganesash@cinj.rutgers.edu.|the Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, and.
authors.forename: Shridar
authors.initials: S
authors.lastname: Ganesan
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D044127:Epigenesis, Genetic; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D033681:Mitochondrial Membrane Transport Proteins; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C570428:CBX8 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D063146:Polycomb-Group Proteins; C511956:TRIM33 protein, human; D014157:Transcription Factors; C491420:Trim33 protein, mouse; C570429:Cbx8 protein, mouse; D063150:Polycomb Repressive Complex 1; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: CBX8; Chromodomain protein; DNA damage; DNA damage response; DNA repair; PARP1; TRIM33; cancer biology; chromatin; polycomb