Reference

Nature Communications, 8: 329. DOI: 10.1038/s41467-017-00374-1 naturensp 420

Authors

Mercè Gomar-Alba, Ester Méndez, Inma Quilis, M. Carmen Bañó & J. Carlos Igual. (Departament de Bioquímica i Biologia Molecular de la Universitat de València i ERI de Biotecnologia i Biomedicina)

Abstract

Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program by G1 CDK-cyclin complexes through the inactivation of Start transcriptional repressors, Whi5 in yeast or Rb in mammals. Here we provide novel keys of how Whi7, a protein related at sequence level to Whi5, represses Start. Whi7 is an unstable protein, degraded by the SCFGrr1 ubiquitin-ligase, whose stability is cell cycle regulated by CDK1 phosphorylation. Importantly, Whi7 associates to G1/S gene promoters in late G1 acting as a repressor of SBF-dependent transcription. Our results demonstrate that Whi7 is a genuine paralog of Whi5. In fact, both proteins collaborate in Start repression bringing to light that yeast cells, as occurs in mammalian cells, rely on the combined action of multiple transcriptional repressors to block Start transition.

Description

La transición entre las fases G1/S, conocida como Start en levadura o punto de restricción en mamíferos, es el punto de control más importante del ciclo celular. Start implica la activación irreversible de un programa transcripcional que al activarse pondrá en marcha una nueva ronda de división celular. Este estudio pone en escena a Whi7 como un nuevo represor del programa transcripcional de Start, demostrando que, como ocurre en mamíferos, las células de levadura también confían en la existencia de múltiples represores transcripcionales para bloquear la transición G1/S.

 

 

Cell Cycle Group

 

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo de Ciclo Celular de la Estructura de Investigación Interdisciplinaria en Biotecnología y Biomedicina de la Universidad de Valencia realiza investigación básica en una de las áreas de mayor interés de la biología molecular y celular, como es el control del ciclo celular. A lo largo de los años se ha centrado en diferentes procesos y ha caracterizado nuevos mecanismos de control de la función de reguladores del ciclo como ciclinas, represores o factores transcripcionales. Actualmente el grupo también trabaja en los mecanismos del checkpoint de integridad del ADN, proceso directamente relacionado con el desarrollo de cáncer.

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