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.

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