Referencia

PLoS Genetics (2013). 9(10): e1003859.doi:10.1371/journal.pgen.1003859.

Autores

Mauricio Valerio-Santiago, Ana Isabel de los Santos-Velázquez, Fernando Monje-Casas

Resumen

When chromosomal DNA is damaged, progression through the cell cycle is halted to provide the cells with time to repair the genetic material before it is distributed between the mother and daughter cells. In Saccharomyces cerevisiae, this cell cycle arrest occurs at the G2/M transition. However, it is also necessary to restrain exit from mitosis by maintaining Bfa1-Bub2, the inhibitor of the Mitotic Exit Network (MEN), in an active state. While the role of Bfa1 and Bub2 in the inhibition of mitotic exit when the spindle is not properly aligned and the spindle position checkpoint is activated has been extensively studied, the mechanism by which these proteins prevent MEN function after DNA damage is still unclear. Here, we propose that the inhibition of the MEN is specifically required when telomeres are damaged but it is not necessary to face all types of chromosomal DNA damage, which is in agreement with previous data in mammals suggesting the existence of a putative telomere-specific DNA damage response that inhibits mitotic exit. Furthermore, we demonstrate that the mechanism of MEN inhibition when telomeres are damaged relies on the Rad53-dependent inhibition of Bfa1 phosphorylation by the Polo-like kinase Cdc5, establishing a new key role of this kinase in regulating cell cycle progression.

Descripción

El “checkpoint” de daños en el ADN (DDC) es un mecanismo de supervivencia que bloquea el ciclo celular en la transición G2/M cuando se detectan lesiones en el material genético. En nuestro artículo hemos demostrado que el correcto funcionamiento del DDC tras la generación de daños en los telómeros requiere adicionalmente la inhibición de la salida de mitosis, que se consigue gracias a la inactivación de Polo quinasa. Esta inhibición, de forma interesante, no es necesaria en respuesta a otros tipos de daños en el ADN

grupo

REFERENCIA DEL GRUPO INVESTIGADOR

Uno de los aspectos clave del ciclo celular es garantizar el correcto reparto del material genético entre las células. Errores en la distribución de los cromosomas determinan la generación de células aneuploides. La aneuploidía es una condición que interfiere con el crecimiento y el desarrollo de los organismos, y que se asocia a distintas enfermedades, entre las que destaca el cáncer. En el laboratorio del Dr. Monje estudiamos los sistemas de vigilancia (“checkpoints”) que las células han desarrollado para evitar problemas durante la segregación cromosómica y, muy especialmente, los mecanismos moleculares por los que estos sistemas regulan el proceso de salida de mitosis.

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

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio Fisher Scientific, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice.

01-07-2017

CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits...

Leer más

Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver

01-06-2017

The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of...

Leer más

Programmed mitophagy is essential for the glycolytic switch during cell differentiation

01-05-2017

Retinal ganglion cells (RGCs) are the sole projecting neurons of the retina and their axons form the optic nerve. Here, we show that embryogenesis-associated mouse RGC differentiation depends on mitophagy...

Leer más

Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes

01-04-2017

The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by...

Leer más

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

01-03-2017

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone...

Leer más

The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

01-02-2017

The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty...

Leer más

Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes

01-01-2017

Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences...

Leer más

A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

01-12-2016

There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways;...

Leer más

In vivo conditional deletion of HDAC7 reveals its requirement to establish proper B lymphocyte identity and development

01-11-2016

Class IIa Histone Deacetylases (HDACs) subfamily members are tissue-specific gene repressors with crucial roles in development and differentiation processes. A prominent example is HDAC7, a class IIa HDAC that shows...

Leer más

DNA demethylation of inflammasome-associated genes is enhanced in patients with cryopyrin-associated periodic syndromes

01-10-2016

Inflammasomes are cytosolic multiprotein complexes in macrophages. They assemble after infection- or stress-associated stimuli, activating both caspase-1-mediated inflammatory cytokine secretion and pyroptosis. Increased inflammasome activity resulting from gene mutations is...

Leer más

Socios Protectores