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Las rupturas de la doble hebra del ADN desencadenan la cohesión de la cromatida hermana en todo el genoma a través de
Elçin Unal1, Jill M Heidinger-Pauli, Douglas Koshland
1Carnegie Institution, Howard Hughes Medical Institute, Department of Embryology, 3520 San Martin Drive, Baltimore, MD 21218, USA.
Science (New York, N.Y.)
|July 14, 2007
Resumen
La cohesión de las cromatidas hermanas se establece independientemente de la replicación del ADN en respuesta a las rupturas de doble cadena de ADN (DSB) a través de Eco1 (Ctf7). Este proceso protege la integridad cromosómica de todo el genoma.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- La cohesina media la cohesión de las cromatidas hermanas, esencial para la segregación cromosómica fiel y la reparación de la ruptura de doble cadena de ADN (DSB).
- Tradicionalmente se pensaba que el establecimiento de la cohesión ocurría exclusivamente durante la replicación del ADN, junto con el replicoma y Eco1 (Ctf7).
Objetivo del estudio:
- Para investigar el mecanismo de generación de cohesión en respuesta a los DSB fuera de la replicación del ADN.
- Para aclarar las funciones duales de Eco1 (Ctf7) en la cohesión y la respuesta al daño del ADN.
Principales métodos:
- Utilizó la levadura en ciernes como un organismo modelo.
- La actividad Eco1 (Ctf7) investigada y el establecimiento de cohesión en respuesta a los DSB en la fase G2/M.
- Se analizó el papel de la actividad de la acetiltransferasa de Eco1 y el punto de control del daño en el ADN.
Principales resultados:
- Se ha demostrado la generación de cohesión dependiente de Eco1 (Ctf7) e independiente de la replicación en respuesta a los DSB en G2/M.
- Se identificaron dos funciones distintas para Eco1 (Ctf7): el establecimiento directo de la cohesión y el desencadenamiento de la cohesión a través de su actividad de acetiltransferasa en respuesta a los DSB y el punto de control del daño del ADN.
- Se observó cohesión inducida por DSB tanto en cromosomas rotos como en cromosomas intactos.
Conclusiones:
- Desafió el modelo establecido al mostrar que la cohesión puede establecerse independientemente de la replicación.
- Destacó el doble papel de Eco1 (Ctf7) en la estabilidad del genoma, vinculando la reparación de DSB y el punto de control del daño del ADN.
- Se propuso que el punto de control del daño del ADN, actuando a través de Eco1 (Ctf7), proporciona protección de la integridad del cromosoma en todo el genoma.
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