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Un mecanismo para la reparación del daño oxidativo en los elementos reguladores de genes

Swagat Ray^1,2,3, Arwa A Abugable^1,2, Jacob Parker^1,4

¹School of Biosciences, University of Sheffield, Sheffield, UK.

|September 28, 2022

Resumen

La proteína del aparato mitótico nuclear NuMA protege a los promotores de genes del daño oxidativo facilitando la reparación del ADN y promoviendo la transcripción. Número de personas

Área de la Ciencia:

Biología molecular
La genética
Biología celular

Sus antecedentes:

El daño oxidativo del genoma es un subproducto del metabolismo celular.
Este daño ocurre en los elementos reguladores de genes durante la transcripción.
La desmetilación epigenética está involucrada en este proceso.

Objetivo del estudio:

Investigar el papel de la proteína del aparato mitótico nuclear (NuMA) en la protección de los promotores del daño oxidativo.
Para aclarar el mecanismo por el cual NuMA media esta protección.
Para entender el papel de NuMA en la transcripción y la reparación del ADN.

Principales métodos:

Evaluar la ocupación genómica de NuMA alrededor de los sitios de inicio de la transcripción.
Análisis de los socios de unión de NuMA, incluidos los componentes de la ARN polimerasa II y la reparación de ruptura de un solo hilo (SSBR).
Investigando el efecto del agotamiento de NuMA en el daño oxidativo y la transcripción.
Utilizando el etiquetado metabólico del ARN naciente para identificar genes dependientes de NuMA.
Pruebas de complementación con mutantes NuMA.

Principales resultados:

NuMA se localiza cerca de los sitios de inicio de la transcripción y se une a la ARN polimerasa II y a los factores SSBR.
El enriquecimiento de NuMA en cromatina aumenta con el daño oxidativo, facilitando el enriquecimiento de TDP1.
El agotamiento de NuMA conduce a un aumento del daño oxidativo del promotor.
NuMA promueve la transcripción mediante la limitación de la poli- ADP-ribosilización de la ARN polimerasa II, aumentando su liberación tras la pausa.
Las células con deficiencia de NuMA presentan defectos de SSBR, que pueden ser restaurados por la complementación.

Conclusiones:

NuMA juega un papel crítico en la protección de los promotores de genes del daño oxidativo del ADN.
NuMA facilita la SSBR en la cromatina dañada y promueve la transcripción.
Este mecanismo es esencial para mantener la integridad del genoma en los elementos reguladores.

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