Inhibition of Ku70 acetylation by INHAT subunit SET/TAF-Iß regulates Ku70-mediated DNA damage response.
Cell Mol Life Sci
; 71(14): 2731-45, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24305947
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-Iß, 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-Iß 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-Iß and Ku70. Furthermore, we demonstrate that overexpressed SET/TAF-Iß inhibits recruitment of Ku70/80 to DNA damage sites. We propose that dysregulation of SET/TAF-Iß expression prevents repair of damaged DNA and also contributes to cellular proliferation. All together, our findings indicate that SET/TAF-Iß interacts with Ku70/80 in the nucleus and inhibits Ku70 acetylation. Upon DNA damage, SET/TAF-Iß dissociates from the Ku complex and releases Ku70/Ku80, which are then recruited to DNA DSB sites via the NHEJ DNA repair pathway.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Daño del ADN
/
Antígenos Nucleares
/
Proteínas de Unión al ADN
/
Chaperonas de Histonas
/
Reparación del ADN por Unión de Extremidades
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Mol Life Sci
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2014
Tipo del documento:
Article