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Una función redox para el grupo [4Fe4S] de la ADN polimerasa de la levadura δ
Phillip L Bartels1, Joseph L Stodola2, Peter M J Burgers2
1Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
Journal of the American Chemical Society
|November 23, 2017
Resumen
El grupo de hierro-azufre en la ADN polimerasa delta de la levadura (Pol δ) es redox-activo. Este grupo actúa como un interruptor, regulando la síntesis de ADN y respondiendo al estrés de replicación.
Área de la Ciencia:
- La bioquímica
- Biología molecular
- La biofísica
Sus antecedentes:
- Un grupo [4Fe4S] en las polimerasas de ADN de la familia B de eucariotas es crucial para formar complejos activos.
- La polimerasa delta de Saccharomyces cerevisiae (Pol δ) es la polimerasa primaria de la cadena rezagada del ADN.
Objetivo del estudio:
- Para investigar la actividad redox del grupo [4Fe4S] en Pol δ.
- Para determinar si este grupo funciona como un interruptor que regula la síntesis de ADN.
Principales métodos:
- Métodos electroquímicos para evaluar la actividad redox.
- Pruebas bioquímicas para medir las tasas de síntesis de ADN.
- Oxidación electroquímica y reducción de Pol δ.
- La fotooxidación mediante el uso de antraquinona atada al ADN.
Principales resultados:
- Pol δ unido al ADN exhibe actividad redox en potenciales fisiológicos.
- La oxidación electroquímica del grupo [4Fe4S] ralentiza significativamente la síntesis de ADN.
- La inhibición de la síntesis de ADN es reversible tras la reducción del racimo.
- La fotooxidación produce resultados similares, confirmando el mecanismo de conmutación redox.
Conclusiones:
- El grupo [4Fe4S] en Pol δ funciona como un interruptor redox.
- Este interruptor proporciona un mecanismo para respuestas rápidas y reversibles al estrés de replicación.
- Comprender esta regulación redox es clave para comprender la fidelidad de la replicación del ADN y la respuesta al estrés.
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