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.

Descárgate este artículo aquí.
Más artículos en la revista SEBBM.

Did you publish an interesting article recently?

Send it through our application form and we will contact you. Age limit: 32.

The selected articles will participate at the Award to the best article of young people of the SEBBM which will be given during SEBBM conference, that will take place at Spain (free registration, travel and accommodation).

More articles of the month

The Helicase PIF1 Facilitates Resection overSequences Prone to Forming G4 Structures

02-11-2018

DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR). The decision between these two routes of DNA repair is...

Read more

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

01-10-2018

The nuclear membrane acts as a mechanosensor that drives cellular responses following changes in the extracellular environment. Mechanically ventilated lungs are exposed to an abnormally high mechanical load that may...

Read more

Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria

03-09-2018

Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear...

Read more

STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis

01-08-2018

The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of...

Read more

A broad atlas of somatic hypermutation allows prediction of activation-induced deaminase targets

02-07-2018

Activation-induced deaminase (AID) initiates antibody diversification in germinal center (GC) B cells through the deamination of cytosines on immunoglobulin genes. AID can also target other regions in the genome, triggering...

Read more

Deciphering the Dynamic Transcriptional and Post-transcriptional Networks of Macrophages in the Healthy Heart and after Myocardial Injury

01-06-2018

Our group is interested in the behavior and transcriptional regulation of macrophages in the context of complex disease environments. We have generated a whole transcriptome dataset (mRNA, miRNA, and lincRNA)...

Read more

Synaptic activity‐induced glycolysis facilitates membrane lipid provision and neurite outgrowth

01-05-2018

La formación de nuevas neuritas es un proceso clave para el correcto desarrollo del sistema nervioso. El crecimiento neurítico requiere la generación de nuevas membranas. No obstante, los cambios metabólicos...

Read more

Mechanisms of bacterial membrane permeabilization by crotalicidin (Ctn) and its fragment Ctn(15-34), antimicrobial peptides from rattlesnake venom.

04-04-2018

La crotalicidina, un péptido del veneno de una serpiente de cascabel, tiene entre otras propiedades una potente acción antimicrobiana. Un fragmento resultante de la disección racional del péptido nativo presenta...

Read more

Functional optimization of broadly neutralizing HIV-1 antibody 10E8 by promoting membrane interactions

01-03-2018

El anticuerpo 10E8 representa uno de los anticuerpos anti-VIH con mayor cobertura de neutralización y potencia descrito a día de hoy. Su epítopo se localiza en una región próxima a...

Read more

Molecular mechanism for the subversion of the retromer coat by the Legionella effector RidL

01-02-2018

La legionelosis o enfermedad del legionario es una neumonía potencialmente fatal, causada por la bacteria Legionella pneumophila. Durante la infección, la bacteria trasloca un gran número de proteínas, llamadas efectores...

Read more

Protector Members