diciembre14Referencia

PNAS 2014 111 (38) E3996-E4005 doi:10.1073/pnas.1408017111

Autores

Marta Muñoz-Barrera and Fernando Monje-Casas

Resumen

Aurora B kinase regulates the proper biorientation of sister chromatids during mitosis. Lack of Aurora B kinase function results in the inability to correct erroneous kinetochore–microtubule attachments and gives rise to aneuploidy. Interestingly, increased Aurora B activity also leads to problems with chromosome segregation, and overexpression of this kinase has been observed in various types of cancer. However, little is known about the mechanisms by which an increase in Aurora B kinase activity can impair mitotic progression and cell viability. Here, using a yeast model, we demonstrate that increased Aurora B activity as a result of the overexpression of the Aurora B and inner centromere protein homologs triggers defects in chromosome segregation by promoting the continuous disruption of chromosome–microtubule attachments even when sister chromatids are correctly bioriented. This disruption leads to a constitutive activation of the spindle-assembly checkpoint, which therefore causes a lack of cytokinesis even though spindle elongation and chromosome segregation take place. Finally, we demonstrate that this increase in Aurora B activity causes premature collapse of the mitotic spindle by promoting instability of the spindle midzone.

Descripción

Durante mitosis, la quinasa Aurora B juega un papel clave asegurando la correcta unión de los cromosomas al huso mitótico. De forma interesante, no sólo la falta de Aurora B representa un problema para las células; un incremento de su actividad quinasa también da lugar a una segregación cromosómica incorrecta y se asocia con varios tipos de cáncer. En nuestro artículo demostramos, usando la levadura Saccharomyces cerevisiae como modelo, que un incremento de la actividad quinasa de Aurora B promueve una desestabilización continua de uniones de los cromosomas al huso, incluso cuando estas uniones son correctas, lo cual causa defectos de segregación cromosómica y activación del “checkpoint” de ensamblaje del huso. Adicionalmente, este incremento de actividad promueve inestabilidad de la zona media del huso y un colapso prematuro del mismo.

grupo

REFERENCIA DEL GRUPO INVESTIGADOR

Durante el ciclo celular, el genoma es fielmente replicado y posteriormente distribuido entre la célula madre y la célula hija. Un reparto equitativo del genoma una vez duplicado es esencial para que cada célula mantenga una copia completa y exacta del genoma. El grupo de investigación del Dr. Monje en CABIMER se centra en el estudio de los mecanismos de vigilancia (“checkpoints”) que garantizan el mantenimiento de la integridad genómica durante la segregación cromosómica. Una segregación incorrecta de los cromosomas puede dar lugar a aneuploidía, una condición que es definida por una alteración del número normal de cromosomas en la célula y que es una marca de cáncer y otras enfermedades.

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