Modelling the Control of DNA Replication in Fission Yeast
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This CellML model runs in both COR and OpenCell to replicate the results in the original published paper. The units have been checked and they are consistent. Please note that this CellML model is based on the equations from the main body of the paper, not the appendix, and so it does not reproduce the cyclical graphs in the paper. The model does however produce results which match the first cycle of the graphs in the paper. Until events can be described in CellML we are unable to capture the switches in this model.
Model Structure
ABSTRACT: A central event in the eukaryotic cell cycle is the decision to commence DNA replication (S phase). Strict controls normally operate to prevent repeated rounds of DNA replication without intervening mitoses ("endoreplication") or initiation of mitosis before DNA is fully replicated ("mitotic catastrophe"). Some of the genetic interactions involved in these controls have recently been identified in yeast. From this evidence we propose a molecular mechanism of "Start" control in Schizosaccharomyces pombe. Using established principles of biochemical kinetics, we compare the properties of this model in detail with the observed behavior of various mutant strains of fission yeast: wee1(-) (size control at Start), cdc13Delta and rum1(OP) (endoreplication), and wee1(-) rum1Delta (rapid division cycles of diminishing cell size). We discuss essential features of the mechanism that are responsible for characteristic properties of Start control in fission yeast, to expose our proposal to crucial experimental tests.
The original paper reference is cited below:
Modeling the control of DNA replication in fission yeast, Bela Novak and John J. Tyson, 1997, Proceedings of the National Academy of Sciences, 94, 9147-9152. PubMed ID: 9256450
cell diagram
A schematic diagram of the reaction mechanism which describes the G1/S and G2/M controls in fission yeast.
Please note that the following switches in the published model are not included in the CellML description:
(i) When SPF crosses 0.1 from below, S phase is initiated (Start).
(ii) When UbE crosses 0.1 from above, the cell divides functionally (mass->mass/2), although visible cytokinesis may be delayed.
(iii) 60 min after Start, kp is divided by 2, and at cell division kp is multiplied by 2.
(taken from Table 1 of the cited reference).
The University of Auckland
The Bioengineering Institute
Rum1
R
Bela
Novak
Initial values for the variables were added to the model. Extra variables were added to create the graphs from the research paper.
This model uses the equations from the main body of the paper, not the appendix, and so does not reproduce the cyclical graphs in the paper. The model does however produce results which match the first cycle of the graphs in the paper.
John
Tyson
J
350
Catherine
Lloyd
May
Proceedings of the National Academy of Sciences USA
Cdc13-P-Cdc2-Rum1 complex
PG2R
Novak and Tyson's 1997 model of the control of DNA replication in
fission yeast.
Catherine
Lloyd
May
c.lloyd@auckland.ac.nz
Jeelean
Lim
added cmeta id's to several variables
Original CellML version of the model
The University of Auckland, Auckland Bioengineering Institute
Jeelean Lim
Modeling the control of DNA replication in fission yeast
94
9147
9152
2003-04-22T00:00:00+00:00
Cdc13-P-Cdc2 complex
PG2
IE
intermediary enzyme
Cdc13-Cdc2-Rum1 complex
G2R
9256450
This CellML version of the model has been checked in COR and PCEnv and the model runs to replicate the results in the original published paper. The units have been checked and are consistent.
Cdc13-Cdc2 complex
G2K
Catherine Lloyd
Fixed bullet points in the documentation.
keyword
DNA replication
cell cycle
yeast
1997-08
2008-12-09T15:08:56+13:00
Cig2-Cdc2 complex
G1K
This is the CellML description of Novak and Tyson's 1997 model of the
control of DNA replication in fission yeast.
2009-02-18T13:53:20+13:00
Cig2-Cdc2-Rum1 complex
G1R
Jeelean
Lim
2007-06-15T10:32:36+12:00