Curr Biol. 2017 Nov 6;27(21):3248-3263.e5. doi: 10.1016/j.cub.2017.09.028 portadaCB


Ana Isabel de los Santos-Velázquez, Inés G. de Oya, Javier Manzano-López, and Fernando Monje-Casas.


The nucleolus plays a pivotal role in multiple key cellular processes. An illustrative example is the regulation of mitotic exit in Saccharomyces cerevisiae through the nucleolar sequestration of the Cdc14 phosphatase. The peculiar structure of the nucleolus, however, has also its drawbacks. The repetitive nature of the rDNA gives rise to cohesion- independent linkages whose resolution in budding yeast requires the Cdc14-dependent inhibition of rRNA transcription, which facilitates condensin accessibility to this locus. Thus, the rDNA condenses and segregates later than most other yeast genomic regions. Here, we show that defective function of a small nucleolar ribonucleoprotein particle (snoRNP) assembly factor facilitates condensin accessibility to the rDNA and induces nucleolar hyper-condensation. Interestingly, this increased compaction of the nucleolus interferes with the proper release of Cdc14 from this organelle. This observation provides an explanation for the delayed rDNA condensation in budding yeast, which is necessary to efficiently coordinate timely Cdc14 release and mitotic exit with nucleolar compaction and segregation.



El nucléolo, además de su función esencial en la biogénesis de los ribosomas, juega también un papel importante en múltiples procesos celulares. Así, en este orgánulo se mantienen secuestradas proteínas clave para la regulación del ciclo celular, que sólo son liberadas cuando se necesita que desempeñen su función. La peculiar estructura del nucléolo supone, no obstante, un inconveniente para las células. La naturaleza repetitiva del ADN ribosómico, alrededor del cual se forma el nucléolo, hace que puedan generarse uniones entre cromosomas que interfieren con su reparto. Con el fin de eliminarlas, las células promueven una condensación del ADN que facilita su compactación. Nuestro estudio demuestra que es necesario un preciso control temporal de la condensación del ADN ribosómico para permitir la distribución equitativa de los cromosomas durante mitosis sin interferir con la correcta progresión del ciclo celular. Adicionalmente, nuestros resultados sugieren que las células podrían utilizar el grado de compactación del nucléolo como un mecanismo para detener la división celular en condiciones adversas, como la falta de nutrientes.






La investigación desarrollada en el grupo del Dr. Monje Casas tiene como objetivo el estudio de la división celular y de los mecanismos de vigilancia que garantizan la correcta distribución del genoma durante este proceso. El grupo está particularmente interesado en desvelar las rutas de señalización que orquestan la progresión del ciclo celular, así como en descifrar los mecanismos moleculares por los que los principales puntos de control celulares regulan estas rutas. Los avances en este campo son extremadamente importantes, ya que resultan esenciales para lograr entender el desarrollo de enfermedades, como el cáncer, que surgen debido a una incorrecta regulación de este proceso.

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