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Participación del complejo de histona acetilasa TIP60 en la reparación del ADN y la apoptosis
T Ikura1, V V Ogryzko, M Grigoriev
1Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|August 31, 2000
Resumen
El complejo de histona acetilasa TIP60, más allá de modificar la cromatina, es crucial para la reparación del ADN y la apoptosis. Las mutaciones que afectan su actividad de acetilasa interrumpen la reparación de la ruptura de doble hebra y la señalización apoptótica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- Las histonas acetilasas son modificadores clave de la cromatina que regulan la transcripción génica.
- La proteína TIP60 es una conocida histona acetilasa involucrada en estos procesos.
Objetivo del estudio:
- Investigar nuevas funciones de las histonacetilasas, específicamente el complejo TIP60.
- Para aclarar el papel de las actividades enzimáticas de TIP60 en los procesos celulares.
Principales métodos:
- Purificación y caracterización del complejo proteico TIP60.
- Evaluación de las actividades complejas de TIP60 que incluyen ATPasa, ADN helicasa y unión al ADN.
- Analizando los efectos del TIP60 mutado (que carece de actividad de la histona acetilasa) en la reparación del ADN y la apoptosis a través de la expresión ectópica.
Principales resultados:
- El complejo TIP60 exhibe actividades de ATPasa, ADN helicasa y de unión al ADN además de la función de la histona acetilasa.
- La expresión ectópica de los mutantes TIP60 deficientes en la actividad de la histona acetilasa condujo a un deterioro de la reparación de la ruptura del ADN de doble hebra.
- Las células que expresan estos mutantes mostraron una pérdida de competencia apoptótica, lo que indica una falla en la señalización de daños en el ADN.
Conclusiones:
- El complejo que contiene TIP60 juega un papel importante en las vías de reparación del ADN.
- La actividad de la histona acetilasa de TIP60 es esencial para la señalización adecuada de la apoptosis en respuesta al daño del ADN.
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