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Una ruptura de dsDNA mediada por topoisomerasa IIbeta requerida para la transcripción regulada
Bong-Gun Ju1, Victoria V Lunyak, Valentina Perissi
1Howard Hughes Medical Institute, Department of Medicine, School of Medicine, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093-0648, USA.
Science (New York, N.Y.)
|June 24, 2006
Resumen
La activación del gen dependiente de la señal requiere la topoisomerasa IIbeta del ADN para crear roturas transitorias del ADN. Este proceso implica enzimas de reparación del ADN y remodelación de la cromatina para la transcripción regulada.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- La epigenética es la epigenética.
- Regulación genética Reglamento genético.
Sus antecedentes:
- La iniciación de la transcripción implica múltiples enzimas, incluida la topoisomerasa II del ADN (Topoisomerasa II).
- La topoisomerasa II se asocia con promotores de genes y puede inducir rupturas de ADN de doble cadena (dsDNA).
- El papel de la topoisomerasa II en la activación de genes regulados no se entiende completamente.
Objetivo del estudio:
- Investigar si la topoisomerasa II del ADN es crítica para la activación de genes dependientes de la señal.
- Aclarar el mecanismo que vincula la actividad de la topoisomerasa II con la regulación transcripcional.
Principales métodos:
- Estudió la transcripción génica dependiente de la señal mediada por receptores nucleares y proteína activadora 1.
- Investigó el requisito de la topoisomerasa IIbeta del ADN en la formación de rupturas de dsDNA.
- Se examinó el papel de la poli (adenosina difosfato-ribosa) polimerasa-1 (PARP-1) y los factores de remodelación de la cromatina.
Principales resultados:
- La transcripción génica dependiente de la señal requiere rupturas transitorias, transitorias y específicas del sitio de dsDNA dependientes de la topoisomerasa IIbeta del ADN.
- Después de las rupturas de dsDNA, se induce la actividad de la poli (adenosina difosfato-ribosa) polimerasa-1.
- Esta cascada facilita la remodelación de los nucleosomas, incluido el intercambio de histonas H1-grupo B de alta movilidad y cambios en la arquitectura de la cromatina.
Conclusiones:
- Las rupturas de dsDNA dependientes de la topoisomerasa IIbeta del ADN son esenciales para la transcripción genética regulada.
- La maquinaria de daño y reparación del ADN, incluida la PARP-1, está vinculada mecánicamente a la activación de genes.
- Este estudio revela un papel novedoso para las roturas de ADN y las vías de reparación en el control de la expresión génica.
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