S1219 residue of 53BP1 is phosphorylated by ATM kinase upon DNA damage and required for proper execution of DNA damage response.
Biochem Biophys Res Commun
; 378(1): 32-6, 2009 Jan 02.
Article
en En
| MEDLINE
| ID: mdl-18996087
53BP1 is phosphorylated by the protein kinase ATM upon DNA damage. Even though several ATM phosphorylation sites in 53BP1 have been reported, those sites have little functional implications in the DNA damage response. Here, we show that ATM phosphorylates the S1219 residue of 53BP1 in vitro and that the residue is phosphorylated in cells exposed to ionizing radiation (IR). Transfection with siRNA targeting ATM abolished IR-induced phosphorylation at this residue, supporting the theory that this process is mediated by the kinase. To determine the functional relevance of this phosphorylation event, a U2OS cell line expressing S1219A mutant 53BP1 was established. IR-induced foci formation of MDC1 and gammaH2AX, DNA damage signaling molecules, was reduced in this cell line, implying that S1219 phosphorylation is required for recruitment of these molecules to DNA damage sites. Furthermore, overexpression of the mutant protein impeded IR-induced G2 arrest. In conclusion, we have shown that S1219 phosphorylation by ATM is required for proper execution of DNA damage response.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Proteínas Serina-Treonina Quinasas
/
Proteínas de Ciclo Celular
/
Proteínas Supresoras de Tumor
/
Péptidos y Proteínas de Señalización Intracelular
/
Proteínas de Unión al ADN
Límite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2009
Tipo del documento:
Article
Pais de publicación:
Estados Unidos