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La acetilación de la cohesión eco1-dependiente durante el establecimiento de la cohesión de la cromatida hermana
Tom Rolef Ben-Shahar1, Sebastian Heeger, Chris Lehane
1Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln'sInn Fields, London WC2A 3PX, UK.
Science (New York, N.Y.)
|July 26, 2008
Resumen
La proteína Eco1 acetila la subunidad Smc3 del complejo de cohesión, promoviendo la cohesión de las cromatidas hermanas durante la replicación del ADN. Este mecanismo de acetilación es crucial para mantener la estabilidad del cromosoma replicado.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología Molecular Biología Molecular
- Genética La genética.
Sus antecedentes:
- Los cromosomas replicados son mantenidos por el complejo de cohesina de la síntesis del ADN a través de la división celular.
- La proteína Eco1 (establecimiento de la cohesión 1) es esencial para este proceso, pero su mecanismo sigue sin estar claro.
Objetivo del estudio:
- Para dilucidar el mecanismo por el cual Eco1 promueve la cohesión de las cromatidas hermanas.
- Identificar los factores y vías que regulan la función de cohesión durante la replicación del ADN.
Principales métodos:
- Cribado genético para los supresores de una mutación eco1-1 sensible a la temperatura en levaduras en ciernes.
- Mutagenesis dirigida al sitio para imitar la acetilación de la subunidad Smc3.
- Análisis de la acetilación y función de la cohesión en cepas de levadura de tipo silvestre y mutantes.
Principales resultados:
- Una mutación que imita la acetilación en Smc3 hace que Eco1 no sea esencial, lo que indica que la acetilación de Smc3 es una función clave de Eco1.
- Smc3 es acetilado por Eco1 durante la replicación del ADN, estabilizando la cohesión de las cromatidas hermanas.
- La inactivación de Wapl (proteína similar a las alas separadas), un antagonista de la cohesión, también suprime eco1-1, lo que sugiere vías paralelas para la cohesión.
Conclusiones:
- Eco1 acetila Smc3 para establecer una cohesión cromática hermana estable durante la replicación del ADN.
- La estabilización de la cohesión por Eco1 actúa en paralelo a una vía de establecimiento de la cohesión independiente de Eco1.
- Comprender el mecanismo de acetilación de Eco1 proporciona información sobre la segregación cromosómica y la estabilidad del genoma.
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