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Los motivos de dedos de zinc que se unen al poli (ADP-ribosa) en las proteínas de reparación del ADN / punto de

Ivan Ahel¹, Dragana Ahel, Takahiro Matsusaka

¹Genetic Recombination and, Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK.

|January 4, 2008

Resumen

Los investigadores descubrieron un nuevo motivo de dedo de zinc (PBZ) de unión de poli-ADP-ribosa crucial para la respuesta al daño del ADN y la poli-ADP-ribosilización de proteínas. Este motivo tiene este motivo.

Área de la Ciencia:

Biología Molecular Biología Molecular
Biología celular Biología celular.
La bioquímica es la bioquímica.

Sus antecedentes:

Las modificaciones post-traducionales (PTM) regulan las funciones de las proteínas, incluidas las interacciones y el reclutamiento de objetivos.
La poli-ADP-ribosilización (PARilación) es un PTM crítico que involucra cadenas de ADP-ribosa, esencial para la reparación del ADN, la estructura cromosómica y la apoptosis.

Objetivo del estudio:

Para identificar nuevos motivos de proteínas involucrados en la poli-ADP-ribosilización.
Para aclarar el papel de estos motivos en la respuesta al daño del ADN y la regulación de los puntos de control.

Principales métodos:

Identificación bioinformática de los motivos proteicos conservados.
Ensayos bioquímicos para demostrar la unión poli (ADP-ribosa) al motivo identificado.
Estudios funcionales utilizando mutantes y inhibidores de proteínas en modelos celulares.

Principales resultados:

Identificación de un nuevo motivo de dedo de zinc (PBZ) de unión a poli-ADP-ribosa en las proteínas eucariotas.
Demostración de la interacción directa entre poli (ADP-ribosa) y el motivo PBZ en las proteínas humanas APLF y CHFR.
El motivo PBZ es esencial para la poli-ADP-ribosilización y la función de CHFR en el punto de control de antifase.

Conclusiones:

El motivo PBZ es un jugador clave en el reconocimiento y la mediación de la poli-ADP-ribosilización.
Este motivo es crítico para la respuesta al daño del ADN y el control del punto de control del ciclo celular.
Dirigirse al motivo PBZ o a la síntesis de PARilación ofrece estrategias terapéuticas potenciales para los trastornos relacionados con el daño del ADN.

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