Modeling of Transcription and DNA Replication
Using the E-CELL Simulation System
Kenta Hashimoto

12

kem@sfc.keio.ac.jp

Fumihiko Miyoshi

t95894fm@sfc.keio.ac.jp

Takeshi Satoyoshi

1323
4

Thomas S. Shimizu

14

tss26@cus.cam.ac.uk

Masaru Tomita

t96457ts@sfc.keio.ac.jp
1

13

13

mt@sfc.keio.ac.jp

Laboratory for Bioinformatics
Graduate School of Media and Governance
Department of Environmental Information
Keio University, 5322 Endo, Fujisawa 252-8520, Japan
Department of Zoology, Cambridge University, CB2 3EJ, UK

1 Introduction
We are currently constructing a \self-replicating" hypothetical cell by integrating models of DNA
replication, transcription and translation, as well as other metabolic pathways, using the E-CELL
simulation system, which is a generic software package for simulation of cellular processes [1]. We
discuss a problem in designing such an integrative model with both transcription and replication; thatis, the problem of DNA polymerase colliding with RNA polymerase when both of them simultaneously
process the same part of chromosome.

2 Transcription
The model of transcription is presented in gure 1. To initiate transcription, RNA polymerase rst
binds to a polymerase binding site on chromosome. Various transcriptional factors promote or suppress
this polymerase binding process. Nucleotides are consumed by the mRNA elongation process, andelongation of mRNA is completed by the transcription termination process. Molecules of mRNA are
degraded spontaneously over time, releasing their nucleotides to the cytoplasm.

3 Replication
Fig. 2 illustrates our model of DNA replication. The process of replication initiation is shown in
the left half of the gure. First, four dnaA proteins bind to dnaA boxes on oriC, forming a dnaAcomplex. Second, DNA polymerase and other replication machinery, such as helicase and gyrase,forms a complex.
Elongation process of replication is shown in the right half of the gure. Chromosome is modeled
as an ordered list of genes and other genomic elements. The elongation process traces the gene list,
and creates copies of the genes one by one. All substances bound to the genes being replicated aretaken o and released into the cytoplasm.

4 Avoiding the Con ict between Transcription and Replication
When RNA polymerase and DNA polymerase are collided on chromosome, the RNA polymerase istaken o and released to the cytoplasm; In this way, we can cope with the \collision" problem. To
implement this, pointers are maintained among substances such as RNA polymerase, transcriptional
factors and binding sites. Grey dotted arrows in gure 1 and gure 2 show the pointers de ned amongsubstances.
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Figure 1: Model of transcription.

Figure 2: Model of replication.

5 Concluding Remarks
We have integrated models of transcription and DNA replication, and coped with the problem ofpolymerase collision by introducing additional book keeping mechanism. We now plan to apply ourmodel discussed above to simulation of genetic network of bacterium phage .

References[1] Tomita, M., Hashimoto, K., Takahashi, K., Shimizu, T., Matsuzaki, Y., Miyoshi, F., Saito, K.,Tanida, S., Yugi, K., Venter, J.C., and Hutchison, C., E-CELL: Software environment for wholecell simulation, Bioinformatics, (to appear).

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