Systems biology of the cell cycle of Saccharomyces cerevisiae: From network mining to system-level properties.
Following a brief description of the operational procedures of systems biology (SB), the cell cycle of budding yeast is discussed as a successful example of a top-down SB analysis. After the reconstruction of the steps that have led to the identification of a sizer plus timer network in the G1 to S transition, it is shown that basic functions of the cell cycle (the setting of the critical cell size and the accuracy of DNA replication) are system-level properties, detected only by integrating molecular analysis with modelling and simulation of their underlying networks. A detailed network structure of a second relevant regulatory step of the cell cycle, the exit from mitosis, derived from extensive data mining, is constructed and discussed. To reach a quantitative understanding of how nutrients control, through signalling, metabolism and transcription, cell growth and cycle is a very relevant aim of SB. Since we know that about 900 gene products are required for cell cycle execution and control in budding yeast, it is quite clear that a purely systematic approach would require too much time. Therefore lines for a modular SB approach, which prioritises molecular and computational investigations for faster cell cycle understanding, are proposed. The relevance of the insight coming from the cell cycle SB studies in developing a new framework for tackling very complex biological processes, such as cancer and aging, is discussed.
Alberghina
Lilia
L
Department of Biotechnology and Biosciences, University of Milano-Bicocca, P.zza della Scienza 2, 20126 Milano, Italy. Electronic address: lilia.alberghina@unimib.it.
Coccetti
Paola
P
Department of Biotechnology and Biosciences, University of Milano-Bicocca, P.zza della Scienza 2, 20126 Milano, Italy.
Orlandi
Ivan
I
Department of Biotechnology and Biosciences, University of Milano-Bicocca, P.zza della Scienza 2, 20126 Milano, Italy.
D002453:Cell Cycle; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D049490:Systems Biology