Video Experimental Relacionado
Updated: Jun 9, 2026
10:55
Study of the DNA Damage Checkpoint using Xenopus Egg Extracts
Published on: November 5, 2012
La fosforilación de MLL por ATR se requiere para la ejecución del punto de control de la fase S de mamíferos
Han Liu1, Shugaku Takeda, Rakesh Kumar
1Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Nature
|September 7, 2010
Resumen
El gen MLL es crucial para el punto de control de la fase S, previniendo el daño del ADN durante la replicación. Su interrupción en las leucemias de MLL conduce a la falla del punto de control y la inestabilidad genómica.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- Biología del cáncer Biología del cáncer.
Sus antecedentes:
- Los puntos de control del ciclo celular son vitales para mantener la integridad genómica mediante la prevención de errores de replicación del ADN.
- La pérdida del control del punto de control contribuye a la inestabilidad genómica y al desarrollo del cáncer.
- Los mecanismos precisos del punto de control de la fase S en los organismos multicelulares requieren una mayor aclaración.
Objetivo del estudio:
- Investigar el papel del gen MLL en el punto de control de la fase S de los mamíferos.
- Para determinar si la disfunción de la MLL contribuye a las leucemias de la MLL.
- Para dilucidar los mecanismos moleculares subyacentes a la función de MLL en la respuesta al daño del ADN.
Principales métodos:
- Análisis de fosforilación de MLL por ATR en respuesta al estrés genotóxico.
- Evaluación de la interacción de MLL con la SCF ((Skp2) E3 ligasa.
- Inmunoprecipitación de la cromatina para estudiar la unión de MLL y la metilación de histonas.
- Análisis fenotípico de células deficientes en MLL y reconstitución mutante de MLL.
- Investigación de las fusiones de MLL en células progenitoras mieloides murinas.
Principales resultados:
- La MLL es fosforilada por ATR en Serina 516 tras el estrés genotóxico, inhibiendo su degradación y llevando a la acumulación.
- La MLL estabilizada metila histona H3 lisina 4 en orígenes de replicación tardía, retrasando la replicación del ADN.
- Las células deficientes de MLL exhiben síntesis de ADN radiorresistente y anomalías genómicas.
- La reconstitución con MLL de tipo salvaje rescata los defectos del punto de control de fase S, mientras que los mutantes no lo hacen.
- Las fusiones de MLL interrumpen la estabilización de MLL mediada por ATR, comprometiendo el punto de control de la fase S.
Conclusiones:
- MLL es un nuevo efector en la red de puntos de control de la fase S de los mamíferos.
- La disfunción del punto de control debido a las alteraciones de MLL es un mecanismo subyacente a las leucemias de MLL.
- La MLL juega un papel crítico en la vía de respuesta al daño del ADN, y su desregulación contribuye a la patogénesis del cáncer.
Más Videos Relacionados
Videos de Conceptos Relacionados
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
02:19The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
02:19The Spindle Assembly Checkpoint
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...