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Quantification of γH2AX Foci in Response to Ionising Radiation
Published on: April 6, 2010
Inestabilidad genómica en ratones carentes de histona H2AXX
Arkady Celeste1, Simone Petersen, Peter J Romanienko
1Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Science (New York, N.Y.)
|April 6, 2002
Resumen
La histona H2AX es crucial para la reparación del ADN. Los ratones que carecen de H2AX exhiben sensibilidad a la radiación, infertilidad y deterioro en el ensamblaje del complejo de reparación del ADN, destacando su papel vital en el mantenimiento de la estabilidad genómica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- Biología celular Biología celular.
Sus antecedentes:
- La estructura de cromatina de orden superior puede impedir el reconocimiento y la reparación de daños en el ADN.
- La fosforilación de la histona H2AX en las rupturas de doble cadena (DSB) está relacionada con el reclutamiento de factores de reparación del ADN.
Objetivo del estudio:
- Investigar el papel fisiológico de la histona H2AX en la respuesta y reparación de daños en el ADN.
- Para determinar las consecuencias de la deficiencia de H2AX in vivo.
Principales métodos:
- Generación y análisis de ratones H2AX knockout (H2AX-/-) con H2AX.
- Evaluación de la sensibilidad a la radiación, puntos de control del ciclo celular, capacidad de reparación del ADN y reclutamiento de factores de reparación en los sitios de daño del ADN.
Principales resultados:
- Los ratones H2AX-/- mostraron sensibilidad a la radiación, retraso en el crecimiento, inmunodeficiencia e infertilidad masculina.
- La inestabilidad cromosómica y los defectos de reparación del ADN se observaron en ratones H2AX-/-.
- Se observó un deterioro en el reclutamiento de Nbs1, 53bp1 y Brca1 a los focos inducidos por la radiación, mientras que el reclutamiento de Rad51 no se vio afectado.
Conclusiones:
- La histona H2AX juega un papel crítico en facilitar el ensamblaje de complejos específicos de reparación del ADN en los sitios de daño del ADN.
- El H2AX es esencial para mantener la estabilidad genómica y las funciones fisiológicas normales, a pesar de no ser necesario para los puntos de control del ciclo celular inducidos por la irradiación.
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