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Kinetic Analysis of a Molecular Model of the Budding Yeast Cell Cycle
The CellML code.
<!-- FILE : chen_model_2000.xml
CREATED : 26th September 2003
LAST MODIFIED : 26th September 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Chen et al.'s kinetic analysis of a molecular model of the budding yeast cell cycle.
CHANGES:
-->
<model xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns="http://www.cellml.org/cellml/1.0#" cmeta:id="chen_csikasz-nagy_gyorffy_val_novak_tyson_2000_version01" name="chen_csikasz-nagy_gyorffy_val_novak_tyson_2000_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling the Budding Yeast Cell Cycle</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
During mitotic cell division, eukaryotic cells will replicate their DNA during the S-phase of the cell cycle, and then divide during the M-phase. S and M phases are temporally separated by gaps, G1 and G2 phases. These discrete phases of the cell cycle are carefully regulated by specific proteins:
</para>
<itemizedlist>
<listitem>
<para>In order to ensure that DNA replication only occurs once per cell cycle, cyclin-dependent protein kinases (CDKs) control the activity of licensing factors, which in turn bind to the DNA and prime the origins of replication. The CDKs ensure that this only occurs once per cycle.</para>
</listitem>
<listitem>
<para>It is also important that the cell doesn't begin to divide until DNA replication is complete. Chromosome alignment during the early M phase is required for the activation of the anaphase-promoting complex (APC). In turn, this initiates the degradation of an inhibitor of chromatid separation. APC also mediates the break down of mitotic cyclins, thereby destroying CDK activities and allowing licensing factors to accumulate and origins to be primed for replication.</para>
</listitem>
<listitem>
<para>Thirdly, the cell must coordinate its DNA replication and division cycle with cell growth. In order to maintain a certain cell size, the cell must reach a critical mass before it divides.</para>
</listitem>
</itemizedlist>
<para>
The majority of dividing eukaryotic cells fulfill these three criteria. However, budding yeast are unusual in that they divide asymmetrically. At the <emphasis>Start</emphasis> of the cell cycle, a bud emerges from the mother cell. S and M phases are completed before the bud can grow as large as the mother cell and consequently, budding produces a large mother cell and a small daughter cell. Following division the daughter cell enters an extended G1 phase during which it has to grow to a critical size before it can produce a bud itself. A second anomaly of yeast budding is that the cells pass through the S and M phases of the cell cycle without their chromatin condensing into discrete chromosomes. In addition, DNA replication does not have to be complete before the cell passes into the M-phase of division.
</para>
<para>
It has been suggested that the budding yeast cycle is an alternation between two self-maintaining states:
</para>
<itemizedlist>
<listitem>
<para>the G1 state in which APC is active, CDK activity is low, and origins are licensed; and </para>
</listitem>
<listitem>
<para>the S/M state in which the APC is inactive, CDK activity is high, and origins are fired and incapable of firing again.</para>
</listitem>
</itemizedlist>
<para>
The G1 state is self-reinforcing because APC destroys S-phase and M-phase cyclins. The S/M state is self-reinforcing because CDKs inactivate APC.
</para>
<para>
In the Chen <emphasis>et al.</emphasis> 2000 publication described here, the authors aim to describe the molecular mechanisms underlying the existence of the two stable states (G1 and S/M), and also the transitions between them. Based on experimental data, they develop a mathematical model of the budding yeast cell cycle (see <xref linkend="fig_reaction_diagram" /> below). This model summarises a vast amount of experimental data, and the model can be used to explore the properties of hypothetical mechanisms.
</para>
<para>
The model has been described here in CellML (the raw CellML description of the Chen <emphasis>et al.</emphasis> 2000 model can be downloaded in various formats as described in <xref linkend="sec_download_this_model" />).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.molbiolcell.org/cgi/content/abstract/11/1/369">Kinetic Analysis of a Molecular Model of the Budding Yeast Cell Cycle</ulink>, Katherine C. Chen, Attila Csikasz-Nagy, Bela Gyorffy, John Val, Bela Novak, and John J. Tyson, 2000, <ulink url="http://www.molbiolcell.org/">
<emphasis>Molecular Biology of the Cell</emphasis>
</ulink>, 11, 369-391. (<ulink url="http://www.molbiolcell.org/cgi/content/full/11/1/369">Full text (HTML)</ulink> and <ulink url="http://www.molbiolcell.org/cgi/reprint/11/1/369.pdf">PDF</ulink> versions of the article are available on the <emphasis>Molecular Biology of the Cell</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10637314&dopt=Abstract">PubMed ID: 10637314</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram</title>
</objectinfo>
<imagedata fileref="../images/chen_model_2000/reaction_diagram.gif" />
</imageobject>
</mediaobject>
<caption>Molecular model of the control of CDK activities during the budding yeast cell cycle.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
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<
CREATED : 26th September 2003
LAST MODIFIED : 26th September 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Chen et al.'s kinetic analysis of a molecular model of the budding yeast cell cycle.
CHANGES:
-->
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling the Budding Yeast Cell Cycle</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
During mitotic cell division, eukaryotic cells will replicate their DNA during the S-phase of the cell cycle, and then divide during the M-phase. S and M phases are temporally separated by gaps, G1 and G2 phases. These discrete phases of the cell cycle are carefully regulated by specific proteins:
</para>
<itemizedlist>
<listitem>
<para>In order to ensure that DNA replication only occurs once per cell cycle, cyclin-dependent protein kinases (CDKs) control the activity of licensing factors, which in turn bind to the DNA and prime the origins of replication. The CDKs ensure that this only occurs once per cycle.</para>
</listitem>
<listitem>
<para>It is also important that the cell doesn't begin to divide until DNA replication is complete. Chromosome alignment during the early M phase is required for the activation of the anaphase-promoting complex (APC). In turn, this initiates the degradation of an inhibitor of chromatid separation. APC also mediates the break down of mitotic cyclins, thereby destroying CDK activities and allowing licensing factors to accumulate and origins to be primed for replication.</para>
</listitem>
<listitem>
<para>Thirdly, the cell must coordinate its DNA replication and division cycle with cell growth. In order to maintain a certain cell size, the cell must reach a critical mass before it divides.</para>
</listitem>
</itemizedlist>
<para>
The majority of dividing eukaryotic cells fulfill these three criteria. However, budding yeast are unusual in that they divide asymmetrically. At the <emphasis>Start</emphasis> of the cell cycle, a bud emerges from the mother cell. S and M phases are completed before the bud can grow as large as the mother cell and consequently, budding produces a large mother cell and a small daughter cell. Following division the daughter cell enters an extended G1 phase during which it has to grow to a critical size before it can produce a bud itself. A second anomaly of yeast budding is that the cells pass through the S and M phases of the cell cycle without their chromatin condensing into discrete chromosomes. In addition, DNA replication does not have to be complete before the cell passes into the M-phase of division.
</para>
<para>
It has been suggested that the budding yeast cycle is an alternation between two self-maintaining states:
</para>
<itemizedlist>
<listitem>
<para>the G1 state in which APC is active, CDK activity is low, and origins are licensed; and </para>
</listitem>
<listitem>
<para>the S/M state in which the APC is inactive, CDK activity is high, and origins are fired and incapable of firing again.</para>
</listitem>
</itemizedlist>
<para>
The G1 state is self-reinforcing because APC destroys S-phase and M-phase cyclins. The S/M state is self-reinforcing because CDKs inactivate APC.
</para>
<para>
In the Chen <emphasis>et al.</emphasis> 2000 publication described here, the authors aim to describe the molecular mechanisms underlying the existence of the two stable states (G1 and S/M), and also the transitions between them. Based on experimental data, they develop a mathematical model of the budding yeast cell cycle (see <xref linkend="fig_reaction_diagram" /> below). This model summarises a vast amount of experimental data, and the model can be used to explore the properties of hypothetical mechanisms.
</para>
<para>
The model has been described here in CellML (the raw CellML description of the Chen <emphasis>et al.</emphasis> 2000 model can be downloaded in various formats as described in <xref linkend="sec_download_this_model" />).
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.molbiolcell.org/cgi/content/abstract/11/1/369">Kinetic Analysis of a Molecular Model of the Budding Yeast Cell Cycle</ulink>, Katherine C. Chen, Attila Csikasz-Nagy, Bela Gyorffy, John Val, Bela Novak, and John J. Tyson, 2000, <ulink url="http://www.molbiolcell.org/">
<emphasis>Molecular Biology of the Cell</emphasis>
</ulink>, 11, 369-391. (<ulink url="http://www.molbiolcell.org/cgi/content/full/11/1/369">Full text (HTML)</ulink> and <ulink url="http://www.molbiolcell.org/cgi/reprint/11/1/369.pdf">PDF</ulink> versions of the article are available on the <emphasis>Molecular Biology of the Cell</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10637314&dopt=Abstract">PubMed ID: 10637314</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
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<caption>Molecular model of the control of CDK activities during the budding yeast cell cycle.</caption>
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