title: Inhibition of Ku70 acetylation by INHAT subunit SET/TAF-Iβ regulates Ku70-mediated DNA damage response.
abstract: DNA double-strand breaks (DSBs) can cause either cell death or genomic instability. The Ku heterodimer Ku70/80 is required for the NHEJ (non-homologous end-joining) DNA DSB repair pathway. The INHAT (inhibitor of histone acetyltransferases) complex subunit, SET/TAF-Iβ, can inhibit p300- and PCAF-mediated acetylation of both histone and p53, thereby repressing general transcription and that of p53 target genes. Here, we show that SET/TAF-Iβ interacts with Ku70/80, and that this interaction inhibits CBP- and PCAF-mediated Ku70 acetylation in an INHAT domain-dependent manner. Notably, DNA damage by UV disrupted the interaction between SET/TAF-Iβ and Ku70. Furthermore, we demonstrate that overexpressed SET/TAF-Iβ inhibits recruitment of Ku70/80 to DNA damage sites. We propose that dysregulation of SET/TAF-Iβ expression prevents repair of damaged DNA and also contributes to cellular proliferation. All together, our findings indicate that SET/TAF-Iβ interacts with Ku70/80 in the nucleus and inhibits Ku70 acetylation. Upon DNA damage, SET/TAF-Iβ dissociates from the Ku complex and releases Ku70/Ku80, which are then recruited to DNA DSB sites via the NHEJ DNA repair pathway.
authors.affiliation: Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul, 156-756, Republic of Korea.
authors.forename: Kee-Beom
authors.initials: KB
authors.lastname: Kim
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Daehwan
authors.initials: D
authors.lastname: Kim
authors.forename: Sangmyung
authors.initials: S
authors.lastname: Rhee
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Seo
mesh_terms: D000107:Acetylation; D034961:Antigens, Nuclear / Q000378:metabolism / Q000502:physiology*; D004249:DNA Damage; D059766:DNA End-Joining Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D057809:HEK293 Cells; D056488:Histone Chaperones / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D000072200:Ku Autoantigen; D008957:Models, Genetic; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; C513473:SET protein, human; D014157:Transcription Factors; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen