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Las rupturas de doble hebra del ADN activan un programa genético multifuncional en el desarrollo de los linfocitos
Andrea L Bredemeyer1, Beth A Helmink, Cynthia L Innes
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Nature
|October 14, 2008
Resumen
Las rupturas fisiológicas de doble hebra del ADN en los linfocitos activan un amplio programa transcripcional más allá de la reparación del ADN. Esta respuesta influye en el desarrollo de los linfocitos y puede ser interrumpida por el daño genotóxico.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Inmunología Inmunología.
- Genética La genética.
Sus antecedentes:
- Las rupturas de doble cadena de ADN (DSB) son lesiones críticas del ADN.
- Las respuestas celulares a los DSB típicamente involucran puntos de control del ciclo celular y vías de supervivencia.
- Los DSB se generan intencionalmente durante el desarrollo de los linfocitos para el ensamblaje genético del receptor de antígenos.
Objetivo del estudio:
- Para investigar la respuesta transcripcional a los DSB fisiológicos durante el desarrollo de los linfocitos.
- Para determinar si esta respuesta difiere de la respuesta DSB canónica.
- Explorar las implicaciones para el desarrollo de linfocitos y el daño genotóxico.
Principales métodos:
- Análisis de la expresión génica en linfocitos murinos.
- Comparación de los perfiles de transcripción después de la inducción fisiológica y genotóxica de DSB.
Principales resultados:
- Los DSB fisiológicos en los linfocitos desencadenan un amplio programa transcripcional.
- Este programa se extiende más allá de los genes de respuesta al daño del ADN canónicos.
- Muchos genes inducidos están involucrados en diversos procesos celulares cruciales para el desarrollo de los linfocitos.
- Algunos patrones de expresión génica se superponen entre las respuestas fisiológicas y genotóxicas de la DSB.
Conclusiones:
- Los DSB fisiológicos actúan como señales de señalización que regulan procesos específicos del tipo de célula más allá del mantenimiento del genoma.
- Los DSB genotóxicos pueden afectar las funciones celulares normales al interferir con estas vías de desarrollo.
- Comprender estos distintos programas de transcripción es vital para la biología de los linfocitos y la toxicología.
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