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The Reproduction of Cells

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I.  The Key Roles of Cell Division

-         Functions in reproduction, growth and repair.

-         Involves the distribution of identical material to two daughter cells.

-         The DNA is pass along without dilution from one generation to another

II.  Cell division distributes identical sets of chromosomes to daughter cells

-         The genome is the cellís total hereditary endowment of DNA.

-         Prokaryotic genomes are often a single long DNA molecule.

-         Eukaryotic genomes consist of several molecules.

-         Typical cell has about 3 meters of DNA in it.

-         The DNA is packaged into chromosomes.

-         Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus.

-         Somatic cells in humans have 46 chromosomes.  Somatic cells are all cells except for sex cells.

-         Sex cells are called gametes and contain only have of the DNA allotment.

-         Incorporated into the chromosome is a very long DNA molecule representing thousands of genes.  It is associated with various proteins that maintain the structure of the chromosome.

-         The DNA-protein complex is called chromatin until it condenses getting ready for division.

-         When chromatin condenses, it becomes densely coiled and folded making chromosomes thick enough to be visible with a microscope.

-         Each duplicated chromosome consists of two sister chromatids.

-         The two chromatids contain identical copies of the chromosomes DNA molecule.

-         In its condensed form, the chromosome has a specialized region called a centromere.

-         Mitosis is the division of the nucleus usually followed immediately by cytokinesis, which is the division of the cytoplasm.

III.  The mitotic cell cycle

-         The cell cycle begins with interphase, which is broken into three subphases.

o       G1 Ė This is known as the gap phase or growth phase.  During this phase, the cell produces proteins and new cell organelles.

o       S Ė This is the synthesis phase.  During this phase, the cell is reproducing its DNA.  It will make exact copies.

o       G2 Ė This is the second gap phase or second growth phase.  During this time the cell is growing in size; making room for the next step.

o       These phases take up the better part of the cell cycle.

-         Mitosis is the next phase, which is broken into five subphases.

o       Prophase is the first subphase.  During this phase, the chromatin condenses to form chromosomes.  The mitotic spindle forms at this time.  This structure is made of microtubules and associated proteins.  While the mitotic spindle assembles, the microtubules used to hold the organelles in place disassemble to provide the material used for the spindles.  The spindles elongate by incorporating the protein tubulin.  This also starts the formation of the centrosome.  In animal cells, the centrioles also begin to form.  The chromosomes or sister chromatids are connected at the kinetochore which is a structure of proteins and specific sections of chromosomal DNA at the centromere.  The two kinetochores face in opposite directions.  Also at this time, the nuclear membrane begins to dissolve.

o       Prometaphase comes next.  At this time, some of the spindle fibers join to the chromosomes at each of the kinetochores.  Once captured, the chromosome begins to move towards the center of the cell. 

o       Metaphase is when the chromosomes are lined up in the middle of the cell at what is known as the metaphase plate.  The spindle is now complete.

o       Anaphase is the separation of the sister chromatids of each chromosome.  The spindle fibers begin moving them towards each of the poles.  This is accomplished as the kinetochore microtubules shorten by depolymerization at the kinetochore ends.

o       During telophase, the spindle fibers that are not connected to the chromosomes begin to push the ends of the cell out to elongate the cell.  At this time, two new nuclear membranes begin to form and nucleoli also reappear.

-         The final phase is cytokinesis.  During this phase, the cytoplasm begins to split.

o       In animal cells, this is the formation of the cleavage furrow, which is a shallow groove in the cell surface near the old metaphase plate.  On the cytoplasmic side of the furrow is a contractile ring of actin microfilaments associated with myosin.  The contraction of the dividing cellís ring of microfilaments deepens the cleavage furrow until the parent cell is pinched in two producing two completely separated cells.

o       In plant cells, the cleavage furrow does not exist.  During telophase, vesicles from the Golgi apparatus move along the microtubules to the middle of the cell where they coalesce producing a cell plat.  Cell-wall materials carried in the vesicles collect in the cell plate as it grows.  The cell plat enlarges until its surrounding membrane fuses with the plasma membrane along the perimeter of the cell.  Two daughter cells result each with its own plasma membrane and cell wall.

IV.  Mitosis in eukaryotes may have evolved from binary fission in bacteria

-         Prokaryotes reproduce by a type of cell division called binary fission. 

-         Most bacterial genes are carried on a single chromosome that consists of circular DNA and associated proteins. 

-         The bacterial chromosome is attached to the plasma membrane.

-         After a bacterial cell replicates its chromosome the two copies remain attached to the cell membrane at adjacent sites. 

-         Growth of the membrane separates the two copies. 

-         When the bacterium has reached twice its initial size, the plasma membrane grows inward dividing the parent cell into two daughter cells.

V.  Regulation of the cell cycle

-         In the early 1970ís it was discovered that the cell cycle was controlled by chemical signals in the cytoplasm. 

-         This is called the cell-cycle control system, which is a cyclically operating set of molecules in the cell that triggers and coordinates key events in the cell cycle.

-         It proceeds on its own and is regulated at certain checkpoints by internal and external controls.

VI.  Cell Cycle Checkpoints

-         A checkpoint in the cell cycle is a critical control point where stop and go ahead signals can regulate the cycle.

-         Animal cells have built-in stop signals that halt the cell until overridden by go-ahead signals.

-         Many of the signals come from surveillance mechanisms that regulate whether or not the process has been completed correctly. 

-         Three major checkpoints are found at G1, G2, and the M phases.

-         The G1 checkpoint is dubbed the restriction point, which seems to be the most important.  If the cell receives the go-ahead signal, the cycle continues and is completed. 

-         If it does not receive the signal, it will exit the cycle switching into a nondividing state called the Go phase.

-         Most of the cells in the human body are in the G0 phase.  These cells include the nerve cells and muscle cells.

-         Some can be called back to the cell cycle by environmental cues.

VII.  The Cell-Cycle Clock: Cyclins and Cyclin Dependent Kinases

-         The regulatory molecules are proteins of two main types.  The protein kinases are enzymes that activate or inactivate other proteins by phosphorylating them.

-         The kinases that drive the cell cycle are actually present at a constant concentration in the growing cell but much of the time they are inactive. 

-         To be active, the kinase must be attached to a cyclin which is a protein that gets its name from constantly being cycled in concentration.  These kinases are called cyclin dependent kinases or Cdks. 

-         The MPF or maturation promoting factor triggers the cells passage past the G2 checkpoint into the M phase.  When cyclins that accumulate during G2 associate with Cdk molecules the resulting MPF complex initiates mitosis. 

-         Later in the M phase, MPF helps switch itself off by initiating a process that leads to the destruction of its cyclin by proteolytic enzymes (protein-hydrolyzing).  These enzymes are also involved in driving the cell cycle past the M-phase checkpoint, which controls the onset of anaphase. 

VIII.  Internal and external cues help regulate the cell cycle

-         Scientists donít know yet what Cdks actually do in most cases.

-         Internal signals:  Messages from the Kinetochores

o       Anaphase does not begin until all the chromosomes are properly attached. 

o       The gatekeeper is the M phase checkpoint that ensures that daughter cells do not end up with missing or extra chromosomes.

o       The signal that delays anaphase originates at the kinetochores that are not yet attached to the spindle fibers.  Certain associated proteins trigger a signaling pathway that keeps an anaphase promoting complex in an inactive state.  Only when the kinetochores are attached does the wait signal cease.  The APC becomes active and the proteolytic enzymes break down the cyclin and the kinetochores separate.

-         External signals Ė growth factors

o       Cells fail to divide if an essential nutrient is left out of the culture medium even if all the other conditions are favorable.

o       A growth factor, which is a protein release by certain body cells that stimulates other cells to divide, is released.

o       One example is the platelet-derived growth factor made by the platelets is important in wound healing.

o       The discovery of growth factors provided the key to understanding density-dependent inhibition, which is a phenomenon in which crowded cells stop dividing.  Apparently when a cell population reaches a certain density, the amount of required growth factors and nutrients becomes insufficient to allow continued cell growth.

o       Animal cells also exhibit anchorage dependence meaning that they must be attached to a substrate.  The anchorage is signaled to the cell cycle control system via pathways involving plasma membrane proteins and elements of the cytoskeleton.

o       Cancer cells exhibit neither.

IX.  Cyclic changes

The restriction point is a point of no return after the S phase begins.

-         After it has committed, it will go through the G2 phase and mitosis regardless of external condition.

-         Some of the molecules that control these phases are called protein kinases, which are enzymes that control the activities of other proteins.

-         A protein kinase activates or inactivates another protein by catalyzing the transfer of a phosphate group from ATP to the target protein and thereby changes its shape to a more active form.

-         This action is controlled by another group of proteins called cyclins (named because they work in a cycle).

-         A protein kinase that controls the cell cycle is only active when it is attached to a particular cycle.  These kinases are referred to as cyclin-dependent kinases or Cdks.

-         MPF is a maturation-promoting factor that is the master switch for a cellís passage from interphase to mitosis.  When cyclins accumulate during G2 of interphase with the protein kinase molecules, the resulting complex initiates prophase and activates the proteins that function in mitosis.

-         Near the end of the mitotic phase, MPF switches itself off by activation an enzyme that destroys cyclin and the Cdk persists in an inactive form until the correct protein kinases are present again.

 

Cancer

Cancer cells do not respond normally to the bodyís control mechanisms.  They divide excessively and invade other tissues.  They do not heed the normal signals that stop growth.  They ignore density-dependent regulation (density increases because of the large numbers of cells and normally shuts down mitosis).  If and when they stop dividing they do so at random points.  They can go on dividing indefinitely if they have a continual supply of nutrients.

 

The potential problem begins when a single cell in a tissue is transformed and is not destroyed by white blood cells.  If it continues to proliferate, it may form a tumor.  If the cells remain in the same site, it is said to be a benign tumor, usually does not cause serious problems, and can be removed completely by surgery.  A malignant tumor becomes invasive enough to impair normal functions of one or more organs.   These cells are unusual because not only do they proliferate at an uncontrollable amount but they may have an abnormal number of chromosomes as well.  This may cause them to lose their attachment to the tissue and begin going through the body and spreading.  The spread of cancer cells beyond their original site is called metastasis.  The treatment for this is usually high-energy radiation and poisonous chemicals.