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Control de la mutagénesis espontánea y la inducida por daño por SUMO y la conjugación de ubiquitina

Philipp Stelter¹, Helle D Ulrich

¹Max Planck Institute for Terrestrial Microbiology, Karl-von-Frisch-Strasse, 35043 Marburg, Germany.

|September 12, 2003

Resumen

Las modificaciones de Ubiquitin y SUMO de PCNA regulan la replicación del ADN y la precisión de la reparación en la levadura. Este estudio revela cómo estos procesos impactan la estabilidad genómica mediante el control de las polimerasas de ADN.

Área de la Ciencia:

Biología Molecular Biología Molecular
Genética La genética.
La bioquímica es la bioquímica.

Sus antecedentes:

La ubiquitina y la SUMO son modificadores de proteínas clave involucrados en diversos procesos celulares eucariotas.
La ubiquitinación y la SUMOilación comparten el mecanismo de conjugación y pueden tener efectos opuestos.
El antígeno nuclear celular proliferante (PCNA) es crucial para la replicación y reparación del ADN, y es modificado tanto por la ubiquitina como por SUMO.

Objetivo del estudio:

Investigar las distintas funciones de la ubiquitina y la modificación SUMO del PCNA en la replicación y reparación del ADN.
Para dilucidar el impacto de la ubiquitinación de PCNA y la SUMOilación en la síntesis de ADN de traslación y la mutagénesis.

Principales métodos:

Se utilizó la levadura como organismo modelo para estudiar la modificación del PCNA.
Se ha investigado la mono-ubiquitinación mediada por RAD6 de PCNA.
Se evaluaron los efectos de la modificación de PCNA en la actividad de las ADN polimerasas eta y zeta.

Principales resultados:

La mono-ubiquitinación mediada por RAD6 de PCNA activa la síntesis de ADN de traslación por las polimerasas eta y zeta.
La actividad de la polimerasa zeta está regulada diferencialmente por la mono-ubiquitina y la modificación SUMO del PCNA.
La ubiquitinación es esencial para la mutagénesis inducida por daño, mientras que tanto la SUMO como la monoubiquitina contribuyen a la mutagénesis espontánea.

Conclusiones:

La modificación SUMO juega un papel durante la fase S del ciclo celular.
Las modificaciones de Ubiquitin y SUMO de PCNA regulan diferencialmente la replicación del ADN y la fidelidad de reparación.
Estos mecanismos reguladores son críticos para mantener la estabilidad genómica general.

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