Positive feedback of G1 cyclins ensures coherent cell cycle entry.
Nature
; 454(7202): 291-6, 2008 Jul 17.
Article
em En
| MEDLINE
| ID: mdl-18633409
ABSTRACT
In budding yeast, Saccharomyces cerevisiae, the Start checkpoint integrates multiple internal and external signals into an all-or-none decision to enter the cell cycle. Here we show that Start behaves like a switch due to systems-level feedback in the regulatory network. In contrast to current models proposing a linear cascade of Start activation, transcriptional positive feedback of the G1 cyclins Cln1 and Cln2 induces the near-simultaneous expression of the approximately 200-gene G1/S regulon. Nuclear Cln2 drives coherent regulon expression, whereas cytoplasmic Cln2 drives efficient budding. Cells with the CLN1 and CLN2 genes deleted frequently arrest as unbudded cells, incurring a large fluctuation-induced fitness penalty due to both the lack of cytoplasmic Cln2 and insufficient G1/S regulon expression. Thus, positive-feedback-amplified expression of Cln1 and Cln2 simultaneously drives robust budding and rapid, coherent regulon expression. A similar G1/S regulatory network in mammalian cells, comprised of non-orthologous genes, suggests either conservation of regulatory architecture or convergent evolution.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
/
Ciclo Celular
/
Fase G1
/
Ciclinas
/
Retroalimentação Fisiológica
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nature
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos