Cell Division: Mitosis

I.  "Life begets life" or "all cells come from pre‑existing cells"
     These phrases, which are an essential part of the cell theory, highlight the biological importance of cell division.

II.  The mechanics of cell division
    The mechanism of cell division varies with the species, but there are a few common features in all organisms:

1. duplication of genetic information (i.e., DNA replication);

2. division of genetic info into daughter cells (i.e., mitosis, meiosis, binary fission);

3. division of the cytoplasm (although this doesn't necessarily occur in all species).

III. Prokaryotic (bacterial) cell division
    Bacterial cells divide by a process called binary fission, which literally means to split in half.  The process is much simpler than in eukaryotic cells, because prokaryotes (1) lack a nucleus and (2) have less genetic information (DNA).  In fact, bacteria have a single circular strand of DNA.  This "chromosome", which is about 500 times longer than an individual cell, must be folded up to fit inside the cell.  The chromosome is attached to the cell membrane.  After the DNA is duplicated, the newly formed strand is also attached to the membrane.  As the cell enlarges it pulls the two chromosomes apart and then the cell pinches off.  See diagram in text.

IV.  Eukaryotic cell division

1. Interphase.  The phase of the cycle during which the cells grows and carries out its normal activities is termed interphase.  Three major events occur during interphase are:  (1) G1, which stands for the first gap phase.  During this portion of the cycle, the cell grows in size, carries out its normal activities and prepares to replicate (make a copy) the DNA; (2) S, which stands for "synthesis", is the phase of the cycle during which DNA is copied (replicated).  Note that there is now twice as much DNA as there was at the begining of interphase; and (3) G2, or the second gap phase.  During G2 the cell prepares for division.  Thus, we can modify our cell cycle:
           G1 → S → G2 → nuclear division (mitosis/meiosis) → cytokinesis → G1 → and so on...
   
        During interphase, the centrosome (which is also called the microtubule organizing center - MTOC) divides as do the centrioles (if present, as in animal cells). This region will be the site of new microtubule formation and serves to anchor the microtubules.

2. Nuclear division by mitosis or meiosis.  This is the phase during which the nucleus divides and the genetic information is parceled out into newly forming daughter cells.  Mitosis results in daughter cells with the same chromosomal number as the original (parent) cell, whereas meiosis results in daughter cells with half the original number of chromosomes.  Meiosis is restricted to sex cells for gamete production, whereas mitosis is responsible for virtually all other cell divisions (i.e. for growth and repair).  We'll first focus on mitosis which occurs in several stages.

• Prophase. Chromosomes become visible, or in other words they condense.  During interphase the DNA strands are uncoiled (uncondensed) in the nucleus.  This uncondensed genetic material is called chromatin; thus an uncondensed chromosome can be called chromatin.  The process of condensing is similar to how a rubber band on a balsa wood airplane gets fatter as the propeller is twisted 'round and 'round.  The condensed DNA, and associated proteins, become the chromosomes. 
  
       Chromosome structure.  The two halves of the chromosome are termed chromatids.  They are attached at a constricted region (centromere).  At the centromere, there are specialized sites, termed the kinetochore, where microtubules will join with the chromosome.
  
       In addition, during prophase, spindle microtubules begin to form near the nucleus on opposite sides.
  
       During late prophase, sometimes considered a separate stage termed prometaphase, the chromosomes become fully condensed, the nuclear envelope begins to disappear, and the spindle, which is a football-shaped aggregation of microtubules, develops.  The microtubules protrude through the nucleus and begin to attach to the kinetochore regions of the chromosomes.  Also,  the MTOC centers/centrosome regions/centrioles their migration to the poles.
   

•  Metaphase.  The nuclear envelope is gone and the chromosomes have aligned along the equator, central axis, of the cell.
   

• Anaphase.  The chromosomes are moved to the poles at a rate of about 1 μm/min.  Two things are responsible for this movement:  (a) microtubules attached to the kinetochores (kinetochore microtubules) become shorter.  Apparently they disassemble at the end near the kinetochore moving the chromosomes closer to the pole; and (b) the cell expands because of the force of spindle microtubules.
   

• Telophase.  The DNA uncondenses, and the nuclei begin to reform. 

        Now, let's modify our cell cycle to include the phases of mitosis:

3. Cytokinesis.  This is the stage during which the cell physically separates into two.  In animals, the cell "pinches" in two.  This occurs in a fashion similar to closing the drawstring on a change purse.  A series of actin microfilaments just beneath the cell membrane serves to divide the cell in two along the cleavage furrow.  In plant cells, which have a rigid wall, they produce another wall between the two new daughter cells.  The newly formed wall is called the cell plate.  The position of the new wall is determined by a band of microtubules that rings the cell prior to division, called the preprophase band of microtubules.

V.  Control of Cell Division

A.  Checkpoint Control
      In order to divide, the cell must pass a certain "start" or checkpoint.  Once past, the cell is committed or obligated to complete the division process.  For most cells, this start point is the transition between G1 and S phases.   Thus, non‑dividing cells are typically arrested in G1 and can temporarily or permanently enter a noncycling state called G0.  There are other controls in G2 (prevent cell from entering mitosis until DNA replicated) and metaphase (prevents anaphase from beginning until chromosomes are aligned).  Start point controls include: 

1. Cell Size, nutrients, growth factors, undamaged DNA.  The cell must reach a certain size or nutrient level, etc to pass the restriction.  Thus cells divide when they reach a certain size which is smart because it prevents cells from getting too large or dividing if they are too small, or have too few nutrients etc.;

2. Contact Inhibition.  For example, normal animal cells in culture will grow until they form a single and contact other cells.  Interestingly, cancer cells have lost this ability.

3. Injury (or other environmental factor).  For example,  liver cells don't normally divide, but can be stimulated to do so by injury; and

4. Cells Can Count.  Normal mammalian cells in culture will only divide about 20‑50 times (sometimes called the Hayflick limit), then the population of cells will die.  Thus, there must be some type of "counting" mechanism.  Many types of cancer cells apparently can't count.  HeLa cells are cancer cells that have divided many times since they were first isolated from Henrietta Lacks in 1951.
   
        How do cells count?  The answer seems to lie in the telomere, which is a cap found on the end of each chromosome.  Like the plastic cap on your shoelace that prevents the shoelace from unraveling, the telomere protects and stabilizes the chromosome.  The telomere region is made of from 1500 - 1600 nucleotides.  The human telomere region is characterized by the repeated sequence of nucleotides, TTAGGG.  It has been demonstrated that the telomere region looses 50 - 200 nucleotides during every division.  Thus the shortening of the telomere may be the actual abacus on which cells are counted; when the telomere gets too short, the cell no longer divides.  Interestingly, cancer cells have shorter, but stable sized telomeres.  But, these cells also possess an enzyme (telomerase) that makes or lengths this region.  In malignant cells that were tested, 90 of 100 had the enzyme telomerase and in immortal cells like HeLa cells, 98/100 have active telomerase.  In contrast, telomerase is only found in normal cells before birth.
   
        To summarize, cancers can be caused by, among other things, cells loosing contact inhibition, failing to stop dividing when they should, and when the normal cycle occurs faster than it should.
    

5. Chemical/Hormonal Regulation.  There are apparently chemicals that signal the cell to divide.  For example, platelet-derived growth factor (PDGF) is required for the growth of fibroblasts (collagen-producing cells) in culture.  PDGF is released upon platelet damage at a site of injury.  PDGF then stimulates fibroblasts to divide to repair the damage.

B.  Cell cycle control
     Once the cell begins to divide, the actions must be carefully choreographed.  At least two major type of proteins are important in this process: cyclins and cyclin-dependent kinases (cdk's).  Their role is to phosphorylate proteins which, in turn, affects cell activity.

VI.  Plants vs. Animals
     The main difference in cell division between plants and animals is cytokinesis (pinching vs. walling).  In addition, animals have centrioles but plants do not. These are apparently not an absolute necessity for cell division.

Last updated: July 14, 2009     � Copyright by SG Saupe