JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks.
Cell Rep
; 16(10): 2641-2650, 2016 09 06.
Article
en En
| MEDLINE
| ID: mdl-27568560
ABSTRACT
The accumulation of damage caused by oxidative stress has been linked to aging and to the etiology of numerous age-related diseases. The longevity gene, sirtuin 6 (SIRT6), promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions. Here we uncover the mechanism by which SIRT6 is activated by oxidative stress to promote DNA double-strand break (DSB) repair. We show that the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on serine 10 in response to oxidative stress. This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs. Our results demonstrate a post-translational mechanism regulating SIRT6, and they provide the link between oxidative stress signaling and DNA repair pathways that may be critical for hormetic response and longevity assurance.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Estrés Oxidativo
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Sirtuinas
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Proteínas Quinasas JNK Activadas por Mitógenos
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Reparación del ADN
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Roturas del ADN de Doble Cadena
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Poli(ADP-Ribosa) Polimerasa-1
Límite:
Animals
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Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article