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El daño en el ADN desencadena la dispersión de Golgi a través de DNA-PK y GOLPH3
Suzette E Farber-Katz1, Holly C Dippold1, Matthew D Buschman1
1Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0707, USA.
Cell
|February 4, 2014
Resumen
El daño en el ADN desencadena la dispersión de Golgi a través del ADN-PK, GOLPH3 y MYO18A. Esta vía afecta la supervivencia celular, con una sobreexpresión de GOLPH3 que confiere resistencia a los agentes que dañan el ADN.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Investigación del cáncer Investigación del cáncer.
Sus antecedentes:
- La respuesta nuclear al daño del ADN está bien caracterizada, regulando la reparación del ADN, la transcripción y el ciclo celular.
- La respuesta citoplasmática al daño del ADN sigue siendo en gran parte inexplorada.
Objetivo del estudio:
- Para investigar la respuesta citoplasmática al daño del ADN.
- Aclarar los mecanismos moleculares subyacentes a la reorganización de Golgi inducida por el daño al ADN y su papel en la supervivencia celular.
Principales métodos:
- Investigó la reorganización de Golgi tras la inducción de daño en el ADN.
- Utilizó técnicas de biología molecular para identificar las proteínas clave involucradas, incluyendo DNA-PK, GOLPH3 y MYO18A.
- Se evaluaron las tasas de supervivencia celular después del daño del ADN en diversas condiciones experimentales (depleción / sobreexpresión de proteínas clave).
Principales resultados:
- El daño en el ADN induce una dramática dispersión de Golgi en todo el citoplasma.
- Esta dispersión es dependiente de la proteína quinasa dependiente del ADN (DNA-PK), GOLPH3, MYO18A y F-actin.
- DNA-PK fosforila GOLPH3, mejorando su interacción con MYO18A y aplicando fuerza al Golgi.
- El agotamiento del ADN-PK, GOLPH3 o MYO18A reduce la supervivencia celular después del daño del ADN.
- La sobreexpresión de GOLPH3, común en los cánceres, confiere resistencia a los agentes que dañan el ADN.
Conclusiones:
- Identificó una nueva vía citoplasmática que involucra al ADN-PK, GOLPH3 y MYO18A en respuesta al daño del ADN.
- Esta vía es crítica para regular la supervivencia celular después del daño del ADN.
- El papel del Golgi en la respuesta al daño del ADN tiene implicaciones para la terapia del cáncer y la comprensión de la progresión de la enfermedad.
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