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La vinculación de la replicación para comenzar por el inhibidor de Cdk Sic11
B L Schneider1, Q H Yang, A B Futcher
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Science (New York, N.Y.)
|April 26, 1996
Resumen
El estudio revela que la inactivación de Sic1 es el papel clave de las ciclinas G1 (Clns) en la división celular de la levadura. La fosforilación y degradación de Sic1 por Clns regulan el compromiso de la replicación del ADN en la transición Start.
Área de la Ciencia:
- Biología celular Biología celular.
- Biología molecular La biología molecular.
- Genética de la levadura genética de la levadura.
Sus antecedentes:
- Tres ciclinas G1 (Clns) regulan el evento de inicio en Saccharomyces cerevisiae, comprometiendo a las células a la división.
- Sic1 es un conocido inhibidor de las cinasas C1b-Cdc28, cruciales para la progresión del ciclo celular.
Objetivo del estudio:
- Para aclarar la función esencial de las ciclinas G1 (Clns) en la división celular de la levadura.
- Investigar el papel de la fosforilación y degradación de Sic1 en la transición Start.
Principales métodos:
- Análisis de los mutantes de Saccharomyces cerevisiae que carecen de ciclinas específicas y Sic1.
- Investigando la fosforilación y degradación de Sic1 en relación con la actividad de Cln.
Principales resultados:
- La fosforilación de Sic1 en el inicio depende de la actividad de Cln.
- La degradación de Sic1 requiere Clns y la enzima Cdc34.4, que conjuga la ubiquitina.
- La inactivación de sic1 es la única función esencial no redundante de Clns, ya que la supresión de sic1 rescata a los mutantes triples cln1 cln2 cln3.
- Los mutantes sic1 exhiben replicación de ADN no acoplada y brotación.
Conclusiones:
- Sic1 es un probable sustrato de los complejos Cln-Cdc28.
- La fosforilación y la posterior proteólisis de Sic1 por Clns son críticas para regular el compromiso con la replicación del ADN en la transición de inicio.
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