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Adaptación de los controles CDC5 y CKII al punto de control de daño del ADN de la levadura
D P Toczyski1, D J Galgoczy, L H Hartwell
1Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Cell
|October 10, 1997
Resumen
Las células de levadura normalmente se adaptan al daño irreparable del ADN, pero dos nuevos mutantes se detienen permanentemente. La eliminación de RAD9 alivió esta detención, implicando a CDC5 y CKB2 en la adaptación al daño del ADN.
Área de la Ciencia:
- Biología celular Biología celular.
- Genética molecular genética molecular.
- Mecanismos de reparación del ADN Mecanismos de reparación del ADN
Sus antecedentes:
- Las rupturas de ADN de doble cadena (dsDNA) desencadenan la detención del ciclo celular en G2/M a través del punto de control de daño del ADN.
- Las células de la levadura pueden adaptarse a roturas irreparables del ADN, anulando el punto de control a pesar del daño persistente.
Objetivo del estudio:
- Identificar los genes involucrados en el proceso de adaptación al daño irreparable del ADN.
- Para caracterizar a los mutantes que no logran adaptarse a las rupturas de dsDNA.
Principales métodos:
- Detección de mutantes de levadura que exhiben una detención permanente de G2/M en respuesta a rupturas irreparables del ADN.
- Análisis genético, incluyendo la deleción de genes y los experimentos de epistasis (por ejemplo, la deleción de RAD9).
- Identificación de genes mutados a través del análisis del locus genético.
Principales resultados:
- Se identificaron dos mutantes con defectos de adaptación, que muestran una detención permanente de G2/M con roturas irreparables de dsDNA.
- El fenotipo de adaptación defectuosa fue suprimido mediante la eliminación de RAD9, un componente clave del punto de control de daño del ADN G2/M.
- Un mutante albergaba una mutación en CDC5 (que codifica una cinasa polo-como), y el otro en CKB2 (que codifica una subunidad de la caseína kinasa II).
Conclusiones:
- CDC5 y CKB2 juegan un papel en la adaptación al daño irreparable del ADN en la levadura.
- Comprender estos genes proporciona información sobre los mecanismos que regulan la adaptación del punto de control del ciclo celular y la tolerancia al daño del ADN.
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