Cell Cycle
Cells must either reproduce or they die. Cells
that can not reproduce and are destined to die
are terminal cells (red blood, nerve cells,
muscles cells etc.). The "life of a cell" is
termed the cell cycle as there are distinct
phases.
Once a cell comes into existence it is in the
G1 or Gap 1. During this time organelles are
reproducing, protein synthesis is occurring for
growth and differentiation. Because,
transcription is occurring, the DNA is uncoiled.
This phase is the most variable, ranging from
almost nothing to years. The average may be
10 hrs.S or
synthesis is the time that DNA is being replicated. There is some
organelle replication as well. This phase ensures that each
emerging daughter cell will have the same genetic content as the
mother cell. G2 or Gap 2 is the time from the end of S until the onset
of mitosis. During this time, the cell is preparing for mitosis. Proteins
are being made and organized for mitosis. A high increase in tubulin
for microtubules for spindle fibers.
Mitosis or cell division, is the period of time that the nucleus and
cytoplasm replicates and divides to produce two genetically identical
daughter cells. The phases are triggered by the accumulation of
control substances called cyclins.
This graph represents the amount of DNA found in the cell
during the cell cycle
A –G1
B- S
C- G2
D- Mitosis
Internal control of the cell cycle
control of the cell cycle is an accumulation “signal molecules”. These signal
molecules must be phosphorylated in order to work. This is a simple model
of how this could occur.
Kinases are proteins (enzymes) that phosphorylate these chemical signals or
enzymes that trigger the cell cycle phases.
This kinase represents the inactive form.
This kinase can take two active forms, the S-form or the M-form and
phosphorylate different chemical signals. It turns out that cell cycle kinases must be activated
by molecules called cyclins.
The kinase can be activated by molecules called cyclins. This represents two different cyclins.
The kinases are called cyclin-dependent-kinases because in order to phosphorylate the chemical
signal, cyclin must be present.
This represents what happens when the cyclins are present.
The kinase can be activated by
molecules called cyclins. This
represents two different cyclins.
The kinases are called cyclindependent-kinases because in
order to phosphorylate the
chemical signal, cyclin must be
present.
This represents what happens
when the cyclins are
present._______________
As the cell goes through the cell cycle, different
cyclins are made to activate the various celldependent-kinases. Once the kinase is activated,
the cyclin is destroyed which deactivates the
kinase. Kinases are not destroyed, they are only
activated or deactivated.
The cell cycle begins. The cell has a certain
amount of cyclin-dependent kinases. The cell
begins to make the S cyclin. The S-cyclin
activates the Cell-dependent-kinase CDK.
The CDK complex phosphorylates the S-signal which will initiate the S-phase to start once it gets
to a critical level. Once the S-signal is phosphorylated, it leaves. This causes the S-cyclin to be
destroyed and the kinase to return to the inactive
state. When there is enough S-signal, then the Sphase will begin. Now the Cdk is inactive, and the
cell begins to make the M-cyclin. The M-cyclin
activates the Cell-dependent-kinase CDK. The
CDK complex phosphorylates the M-signal which
will initiate the M-phase to start once it gets to a
critical level. This complex is called the
maturation-promoting-factor (MPF). Once the Msignal is phosphorylated, it leaves. This causes
the M-cyclin to be destroyed and the kinase to
return to the inactive state. When there is enough
M-signal, then the M-phase will begin.
Various cyclins are made and destroyed
throughout the cell cycle whereas the level of cell
division kinases remain constant. Kinases
however are activated by various cyclins and the
activity are mirrored by the rise and fall of cyclins.
Fluctuations in concentration of cyclins allow for cell
cycle checkpoints. The three major check points
are G1/S , G2/M and Spindle checkpoints. These
checkpoints have build-in-stop signals that hold the
cell cycle at the checkpoint until overridden by goahead signals.
This is a textbook’s diagram of how cyclins and
kinases in the cell cycle work.
Three major checkpoints
1. G1/S (R point) checkpoint is the primary
determining factor for cell division to take place.
Growth factors are affecting the cell cycle, and cells
are growing. Once the R point is passed the DNA is
going to be replicated. If a cell receives a go-ahead
signal at this check-point, it will complete the cell cycle
and divide. However, if the cell does not receive the
go-ahead signal in G1, the switches to a nondividing
state called G0.
2. This checkpoint represents the commitment for
starting the process of mitosis. This checkpoint also ensures that the DNA has been replicated
correctly. If the DNA has been damaged, then the
cell does not continue to mitosis. Once the Cdk
and cyclin combine, it is called “mitosis promoting
factor” or MPF.
3. The M/ spindle check point ensure that all the
chromosomes are attached to the spindle in
preparation of mitosis. The separation of the
chromatids are irreversible. Once chromatids are
replicated they are held together by a protein
substance called cohesion protein. Another protein
called seperase will destroy this protein. Seperase
is inhibited or unable to destroy cohesion because
of third protein called securin which seperase
inactive. So in effect the APC (anaphase
promoting complex) activates securin, which
actives an enzyme seperase to destroy cohesion.
In many cells this occurs Once chromatids are
replicated they are held together by a protein
substance called cohesion protein. Another protein
called seperase will destroy this protein. Seperase
is inhibited or unable to destroy cohesion because
of third protein called securin which seperase
inactive. So in effect the APC (anaphase
promoting complex) activates securin, which
actives an enzyme seperase to destroy cohesion. In many cells this occursOften the G1 check
point or "restriction point" in mammalian cells seems to be the most important one. If a cell
receives a go-ahead signal at this check-point, it will complete the cell cycle and divide. However,
if the cell does not receive the go-ahead signal in G1, the switches to a nondividing state called
G0. There has been several discoveries1. External Signals-This include certain chemical and
physical factors that affect cell division. Mammalian cells need certain nutrients and regulatory
proteins or growth factors are needed for cell division. For example, when the skin has been
damage (wound), platelets release a substance called platelet-derived growth factor (PDGF).
This growth factor stimulate fibroblast cells to start to reproduce and make scar tissue.
External signals can effect how cells grow in culture.
Density-dependent inhibition- cells in culture stop dividing when they become crowded forming a
single layer of cells. It seems that when crowded, there is insufficient growth factor produced and
nutrients for cell division to continue.
Anchorage dependence- mammalian cells need to be attached to substratum like the inside of a
culture jar or other tissue in order to reproduce. This phenomenon is linked to a control system
attached to the plasma membrane proteins and the cytoskeleton. These phenomenons keep the
growth of tissue in check.
Cancer cells do not exhibit density-dependent inhibition or anchorage dependence.