原创力文档a quantitative model of the initiation of dna replication in saccharomyces cerevisiae predicts the effects of system perturbations一个定量模型在酿酒酵母dna复制起始的预测系统扰动的影响.pdfVIP
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Gidvani et al. BMC Systems Biology 2012, 6:78
/1752-0509/6/78
RESEARCH ARTICLE Open Access
A quantitative model of the initiation of DNA
replication in Saccharomyces cerevisiae predicts
the effects of system perturbations
1 2 2 1 1 1*
Rohan D Gidvani , Peter Sudmant , Grace Li , Lance F DaSilva , Brendan J McConkey , Bernard P Duncker
and Brian P Ingalls1,2*
Abstract
Background: Eukaryotic cell proliferation involves DNA replication, a tightly regulated process mediated by a
multitude of protein factors. In budding yeast, the initiation of replication is facilitated by the heterohexameric
origin recognition complex (ORC). ORC binds to specific origins of replication and then serves as a scaffold for the
recruitment of other factors such as Cdt1, Cdc6, the Mcm2-7 complex, Cdc45 and the Dbf4-Cdc7 kinase complex.
While many of the mechanisms controlling these associations are well documented, mathematical models are
needed to explore the network’s dynamic behaviour. We have developed an ordinary differential equation-based
model of the protein-protein interaction network describing replication initiation.
Results: The model was validated against quantified levels of protein factors over a range of cell cycle timepoints.
Using chromatin extracts from synchronized Saccharomyces cerevisiae cell cultures, we were able to monitor the in vivo
fluctuations of several of the aforementioned proteins, with additional data obtained from the literature. The model
behaviour conforms to perturbation trials previously reported in the literature, and accurately predicts the results of our
own knockdown experiments. Furthermore, we successfully incorporated our replication initiation model into an
established model of
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