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Nat Commun ; 7: 11161, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-27045731

RESUMO

Cell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires the periodic expression of particular gene clusters in different cell cycle phases. However, the interplay between the networks that generate these transcriptional oscillations and the core cell cycle machinery remains largely unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate that periodic expression is governed by quantitative changes in Cdk1 activity, with different clusters directly responding to specific activity levels. We further establish that cell cycle events neither participate in nor interfere with the Cdk1-driven transcriptional program, provided that cells are exposed to the appropriate Cdk1 activities. These findings contrast with current models that propose self-sustained and Cdk1-independent transcriptional oscillations. Our work therefore supports a model in which Cdk1 activity serves as a quantitative platform for coordinating cell cycle transitions with the expression of critical genes to bring about proper cell cycle progression.


Assuntos
Proteína Quinase CDC2/genética , Ciclo Celular/genética , Regulação Fúngica da Expressão Gênica , Proteínas de Schizosaccharomyces pombe/genética , Schizosaccharomyces/genética , Transcrição Gênica , Proteína Quinase CDC2/metabolismo , Ciclo Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Família Multigênica , Periodicidade , Purinas/farmacologia , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Transdução de Sinais
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