Chapter 18 – The cell division cycle
Cell cycle; cycle of duplication and division
Overview of the cell cycle
Most basic function
• Duplicate the DNA, other macromolecules and organelles
• Segregate the DNA into 2 identical daughter cells
The eukaryotic cell cycle usually includes four phases
M phase;
• Mitosis; nucleus divides/separation of chromosomes
• Cytokinesis; cell splits in two (cytoplasm divides)
Interphase;
• G1 phase; cell growth, transcription & translation, new organelles
• S-phase; DNA replication
• G2 phase; cell growth, condensation of chromosomes
At point in G1 and G2 a cell decides whether to proceed to the next phase or pause.
A cell-cycle control system triggers the major processes of the cell cycle
There is a cell cycle control system to ensure that they replicate all their DNA and
organelles before they move further.
3 Checkpoints; transition points (overgangspunten);
• From G1 to S phase; the system control if the environment is favorable for
proliferation before committing to DNA replication. Cell proliferation requires
sufficient nutrients and specific signal molecules in the environment. What
they can do
o Delay progress through G1
o Go to resting state G0
• From G2 to M phase; confirms that DNA is undamaged and fully replicated
AND is the environment favorable?
• During mitosis (metaphase to anaphase); control that the duplicated
chromosomes are properly attached to a cytoskeletal machine (mitotic
spindle)
The cell-cycle control system
The cell-cycle control system depends on cyclically activated protein
kinases called cdks
Cell cycle use phosphorylation followed by dephosphorylation to switch the
activity of proteins in cells on and off.
Phosphorylation is carried out by protein kinases
Dephosphorylation is carried out by protein phosphatase
When protein kinases are present, they are activated after which they are quickly
inactive. For example, become active toward the end of G1 phase and are
responsible for driving the cell into the S phase.
, Switching on and off these kinases is responsibility of cyclins
These cyclins have no enzymatic activity, but they need to bind to cell-cycle kinases
before the kinases can become active. The kinases of the cell-cycle system are
therefore cyclin-dependent protein kinases (Cdks). Now cyclin can be enzymatically
active.
Different cyclin-Cdk complexes trigger different steps in the cell cycle
There are several types of cyclin and Cdks, so different complex triggers
different steps in the cell cycle.
• M-cyclin; cyclin that acts in G2 to trigger entry into M phase.
Complex = M-Cdk
• S-cyclin; cyclin that acts in the G1 to trigger entry into the S phase.
Complex= S-Cdk
• G1/S-cyclin; cyclin that acts in the G1 to trigger entry into the S phase.
Complex = G1/S- Cdk. EERDER IN THE G1!
• G1-cyclin; drives it through the G1 phase
Each cyclin-Cdk complex phosphorylates at different target protein.
Cyclin concentrations are regulated by transcription and by proteolysis
Over the course of the cell cycle the concentration of each type of cyclin rises and
then falls.
Increase; from transcription of cyclin genes
Fall; destruction (afbraak) of the protein
Destruction of S and M cyclin half way through M phase depends on large enzyme
complexes → Anaphase-promoting complex (APC).
These mark the cyclins with chain of ubiquitin.
The cyclins are destructed
The Cdk returns to an inactive state
The activity of Cyclin-Cdk complexes depends on phosphorylation and
Dephosphorylation
So, the activity of Cdks can be modulated by phosphorylation and
dephosphorylation but also by the binding of Cdk inhibitor proteins.
They are used to block the activity of cyclin-Cdk complexes.
When they are in inactive state during G1 phase they delay the
process in S phase.
So, the checkpoints are regulated by cyclins.
The cell-cycle control system can pause the cycle in various ways
The various ways are;
• From G1 to S; Cdk inhibitors block entry to S phase
• From G2 to M; inhibition of activation phosphate required to entry the Cdk
• In mitosis; inhibition (remming) of APC activation delays exit from mitosis
G1 phase
2 options in the G1 phase
Cell cycle; cycle of duplication and division
Overview of the cell cycle
Most basic function
• Duplicate the DNA, other macromolecules and organelles
• Segregate the DNA into 2 identical daughter cells
The eukaryotic cell cycle usually includes four phases
M phase;
• Mitosis; nucleus divides/separation of chromosomes
• Cytokinesis; cell splits in two (cytoplasm divides)
Interphase;
• G1 phase; cell growth, transcription & translation, new organelles
• S-phase; DNA replication
• G2 phase; cell growth, condensation of chromosomes
At point in G1 and G2 a cell decides whether to proceed to the next phase or pause.
A cell-cycle control system triggers the major processes of the cell cycle
There is a cell cycle control system to ensure that they replicate all their DNA and
organelles before they move further.
3 Checkpoints; transition points (overgangspunten);
• From G1 to S phase; the system control if the environment is favorable for
proliferation before committing to DNA replication. Cell proliferation requires
sufficient nutrients and specific signal molecules in the environment. What
they can do
o Delay progress through G1
o Go to resting state G0
• From G2 to M phase; confirms that DNA is undamaged and fully replicated
AND is the environment favorable?
• During mitosis (metaphase to anaphase); control that the duplicated
chromosomes are properly attached to a cytoskeletal machine (mitotic
spindle)
The cell-cycle control system
The cell-cycle control system depends on cyclically activated protein
kinases called cdks
Cell cycle use phosphorylation followed by dephosphorylation to switch the
activity of proteins in cells on and off.
Phosphorylation is carried out by protein kinases
Dephosphorylation is carried out by protein phosphatase
When protein kinases are present, they are activated after which they are quickly
inactive. For example, become active toward the end of G1 phase and are
responsible for driving the cell into the S phase.
, Switching on and off these kinases is responsibility of cyclins
These cyclins have no enzymatic activity, but they need to bind to cell-cycle kinases
before the kinases can become active. The kinases of the cell-cycle system are
therefore cyclin-dependent protein kinases (Cdks). Now cyclin can be enzymatically
active.
Different cyclin-Cdk complexes trigger different steps in the cell cycle
There are several types of cyclin and Cdks, so different complex triggers
different steps in the cell cycle.
• M-cyclin; cyclin that acts in G2 to trigger entry into M phase.
Complex = M-Cdk
• S-cyclin; cyclin that acts in the G1 to trigger entry into the S phase.
Complex= S-Cdk
• G1/S-cyclin; cyclin that acts in the G1 to trigger entry into the S phase.
Complex = G1/S- Cdk. EERDER IN THE G1!
• G1-cyclin; drives it through the G1 phase
Each cyclin-Cdk complex phosphorylates at different target protein.
Cyclin concentrations are regulated by transcription and by proteolysis
Over the course of the cell cycle the concentration of each type of cyclin rises and
then falls.
Increase; from transcription of cyclin genes
Fall; destruction (afbraak) of the protein
Destruction of S and M cyclin half way through M phase depends on large enzyme
complexes → Anaphase-promoting complex (APC).
These mark the cyclins with chain of ubiquitin.
The cyclins are destructed
The Cdk returns to an inactive state
The activity of Cyclin-Cdk complexes depends on phosphorylation and
Dephosphorylation
So, the activity of Cdks can be modulated by phosphorylation and
dephosphorylation but also by the binding of Cdk inhibitor proteins.
They are used to block the activity of cyclin-Cdk complexes.
When they are in inactive state during G1 phase they delay the
process in S phase.
So, the checkpoints are regulated by cyclins.
The cell-cycle control system can pause the cycle in various ways
The various ways are;
• From G1 to S; Cdk inhibitors block entry to S phase
• From G2 to M; inhibition of activation phosphate required to entry the Cdk
• In mitosis; inhibition (remming) of APC activation delays exit from mitosis
G1 phase
2 options in the G1 phase
