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Biofundamentals - Cell Growth and Cell Division
11/16/08 9:43 PM
Cell growth & division
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Perhaps the most characteristic feature of life is the ability to
replicate, to make copies of itself.
During the process of cell replication, the genetic material must be
replicated. The two strands of the DNA molecule separate locally,
and each serves as a template for generating a new strand.
Changes in the DNA that accumulate prior to, or which occur during
replication, are passed on to the daughter cells.
These daughter cells are built by capturing energy and matter from
the environment.
If we inoculate a culture with a few bacteria, within a few
hours they will have transformed components of the
medium into millions of copies of themselves.
If we look at these cells with a microscope, we find that they
do not grow haphazardly.
They appear remarkably
uniform in both size and
shape. Different types of
cells have different
shapes.
They grow to a certain
size and then divide.
Cells monitor and control their size.
For example, consider the single celled eukaryote,
Amoeba proteus – these organisms divide only after
they have grown to a characteristic size.
Using microsurgical methods, it is possible to keep
cells small by simply repeatedly cutting off parts of the
cell. After the cell heals, it grows.
If you do this repeatedly, the cell grows but never
divides. This type of experiment argues that the cell
does not use time to decide to divide, but rather size.
How does the cell know when it has reached the
correct size, how does it known when to divide?
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correct size, how does it known when to divide?
Studies on yeasts (unicellular eukaryotes) have identified mutations that lead to
cells that are consistently larger or smaller than the usual, or wild type phenotype.
The ability to find such mutations implies that an active, genetically encoded system
controls when cells divide.
In amoeba, what experiment suggested that a cell must reach a
certain size before it divides? What might the controls be for
such an experiment?
Consider a culture of bacteria, which might have an evolutionary
advantage, a mutation that leads to cells that are larger or smaller
than normal?
What factors might determine optimal cell size?
Bacterial cell cycles: The replication of a cell, or an organism, can be thought of as
a cycle. Somewhat arbitrarily, we place the beginning of this cycle with the decision
to replicate the genetic material, the DNA.
This is a critical decision for the cell. DNA replication involves the unwinding of the
DNA and a set of highly interdependent and coordinated processes.
Consider the following catastrophic scenario. A cell begins replicating its DNA, but
before it completes the process it runs out of resources -- ATP levels fall and the
other deoxyribonucleotide triphosphates needed to synthesize DNA are in short
supply.
Under these conditions replication forks will stop and the DNA will be left unwound
and incompletely replicated. This is a situation that is likely to lead to DNA
damage.
To avoid this possibility, cells tightly
regulate the initiation of DNA
replication.
This decision is known as start; once
made, the cell begins on the path to
DNA replication.
In bacteria start involves the molecular
decision to build a replication
initiation complex.
The initiation complex consists of
proteins that associate with a specific
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proteins that associate with a specific
DNA sequence, the origin of
replication or origin.
There is a single origin in the bacterial
chromosome and acts like a gene. In E.
coli this gene is called OriC. For a DNA
molecule to replicate, it must have at
least one functional origin of replication.
In most prokaryotes, the chromosome is
a circular DNA molecule. This is where
the replication bubble initiates; the two
replication forks move away from one
another and around the chromosome.
The forks collide in the region of the
chromosome known as the terminator
or ter.
At the end of replication, two sister
chromosomes are entangled with one
another, they are concatenated.
They are untangled by the enzyme
topoisomerase, which can pass one
double-stranded DNA molecule through
another.
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Once the replicated chromosomes are separated,
the cell can be divided into two.
A septum assembles at the center of the cell.
This molecular "purse string" is linked to the inner
surface of the plasma membrane.
As it contracts, it pulls the membrane together and
separates the two cells.
When growing under optimal conditions bacteria can
divide as fast as once every 15 to 20 minutes.
Even though it does not produce a product, it is possible to view
OriC as a gene. What happens to a bacterial cell if there is a
mutation in OriC?
The eukaryotic cell cycle: The most dramatic event
in the eukaryotic cell cycle, the one that caught the
eye of early microscopists, is the drastic change in
nuclear organization associated with cell division.
This process of chromosome segregation is known
as mitosis.
As the cell enters mitosis, chromosomes appear as
distinct bodies.
While most prokaryotic cells have a single circular chromosome, most eukaryotes
have multiple linear chromosomes, and each chromosome has multiple origins
of replication. Each chromosome is a single DNA molecule.
The DNA in each chromosome must be completely replicated and the copies
segregated so that each daughter cell receives one and only one complete copy of
each chromosomal DNA molecule.
The complexity of the eukaryotic cell, makes mitosis and cell division, known as
cytokinesis, more mechanically intricate than the analogous processes in
prokaryotes.
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As in the case of bacterial cells
(above), eukaryotes have a cell
cycle.
Start is located in the period known
as the G 1 phase of the cell cycle; the
period during which DNA synthesis
occurs is known as S phase.
The period between the end of S and
the beginning of mitosis is known as
G 2 phase of the cell cycle.
Mitosis itself is known as M phase.
The length of the cell cycle can various tremendously, from hours to years.
Cells that are not actively dividing are said to be in G o. Some cells enter G o and
never divide again – these cells are said to be terminally differentiated.
We will leave the mechanical and molecular details of mitosis and cytokinesis to
more advanced classes in cell biology; what is critical to understand here is that
they provide a complete copy of the genome to each daughter cell (mitosis) and they
divide the cell into two (cytokinesis).
Checkpoints: The process of chromosome replication and segregation is so critical
to the future of the replicated cell that its accuracy is checked in a number of ways.
There is a DNA damage checkpoint that inhibits DNA replication until damaged DNA
is repaired.
The process of chromosome replication, segregation and cell division is more
complex in eukaryotes, and so there are more possibilities for error.
There are correspondingly more checkpoints. These include
checking that DNA synthesis is complete
checking that the DNA is undamaged, and that if damaged, repaired
checking that all of the chromosomes are attached to the molecular machinery
that segregates chromosomes to daughter cells, the mitotic spindle.
The DNA replication and repair checkpoints are located throughout
interphase (G 1 S and G 2 ) while the checkpoints associated with
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chromosome segregation are located in M phase.
What happens to the two daughters if mitosis is not accurate, e.g.
if one cell receives two copies of a chromosome, while the other
receives none?
What would happen if the cell divides before DNA replication is
completed?
What might happen, if a cell arrests at a checkpoint, but cannot fix
the problem? Is this a serious problem for unicellular organisms?
how about multicellular organisms?
Use Wikipedia | revised 16-Nov-2008
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